Background In patients with type 1 diabetes mellitus who donot have uremia and have not received a kidney transplant, pancreastransplantation does not ameliorate established lesions of diabeticnephropathy within five years after transplantation, but theeffects of longer periods of normoglycemia are unknown.
Methods We studied kidney function and performed renal biopsiesbefore pancreas transplantation and 5 and 10 years thereafterin eight patients with type 1 diabetes but without uremia whohad mild to advanced lesions of diabetic nephropathy at thetime of transplantation. The biopsy samples were analyzed morphometrically.
Results All patients had persistently normal glycosylated hemoglobinvalues after transplantation. The median urinary albumin excretionrate was 103 mg per day before transplantation, 30 mg per day5 years after transplantation, and 20 mg per day 10 years aftertransplantation (P=0.07 for the comparison of values at baseline and at 5 years; P=0.11 for the comparison between baseline and 10 years). The mean (±SD) creatinine clearancerate declined from 108±20 ml per minute per 1.73 m2 ofbody-surface area at base line to 74±16 ml per minuteper 1.73 m2 at 5 years (P<0.001) and 74±14 ml perminute per 1.73 m2 at 10 years (P<0.001). The thickness ofthe glomerular and tubular basement membranes was similar at5 years (570±64 and 928±173 nm, respectively)and at base line (594±81 and 911±133 nm, respectively)but had decreased by 10 years (to 404±38 and 690±111nm, respectively; P<0.001 and P=0.004 for the comparisonswith the base-line values). The mesangial fractional volume(the proportion of the glomerulus occupied by the mesangium)increased from base line (0.33±0.07) to 5 years (0.39±0.10,P=0.02) but had decreased at 10 years (0.27±0.02, P=0.05for the comparison with the base-line value and P=0.006 forthe comparison with the value at 5 years), mostly because ofa reduction in mesangial matrix.
Conclusions Pancreas transplantation can reverse the lesionsof diabetic nephropathy, but reversal requires more than fiveyears of normoglycemia.
Diabetic nephropathy is the single most important cause of end-stagerenal disease.1 It results from the gradual accumulation ofextracellular matrix in glomerular and tubular basement membranesand mesangial and interstitial tissues, as well as from hyalinosisof glomerular arterioles and global glomerular sclerosis.2,3,4,5,6Hyperglycemia is a necessary precondition for the developmentof lesions of diabetic nephropathy.7,8,9,10 The Diabetes Controland Complications Trial demonstrated a reduced incidence ofmicroalbuminuria in patients with type 1 diabetes mellitus whoreceived intensive treatment rather than standard treatment.11In other, similar studies, intensive therapy resulted in lessaccumulation of mesangial matrix during a 5-year period in patientswho had received renal allografts12 and reduced thickening ofthe glomerular basement membrane over a period of 18 to 24 monthsin patients who had not received grafts.13 Moreover, in patientswith diabetes, successful pancreas transplantation two to fouryears after kidney transplantation was associated four to sixyears later with less mesangial expansion than was observedafter kidney transplantation alone.14
It has not been possible, however, to demonstrate that long-termnormoglycemia after pancreas transplantation can reverse establishedlesions of diabetic nephropathy. In 13 patients with their ownkidneys who had established lesions and were studied five yearsafter pancreas transplantation, we found no amelioration ofbase-line glomerular structural abnormalities.15 We studiedthe same group of patients after 10 years of normoglycemia,with a focus on thickening of the glomerular and tubular basementmembranes and mesangial expansion.
Methods
Patients and Study Protocol
The study subjects were eight patients who had type 1 diabetesand lesions of diabetic nephropathy (but not uremia) who hadreceived pancreas transplants and had been insulin-independentfor at least 10 years after transplantation (Table 1). Of theoriginal cohort of 13 patients who were evaluated at the 5-yearfollow-up,15 2 subsequently received kidney transplants 6 and8 years after pancreas transplantation, 2 lost pancreatic-graftfunction and required insulin therapy, and 1 declined to participatein the 10-year follow-up studies. Among the remaining eightpatients, four had received cadaveric pancreas grafts and fourhad received segmental pancreas grafts from living related donors(three from HLA-identical siblings), as previously reported.16,17One patient had partial graft rejection two years after transplantation,necessitating the reinstitution of insulin therapy; a secondgraft was successfully transplanted, and insulin was discontinuedthree months later. In the first year after transplantation,one patient had one successfully treated rejection episode andone patient had two; five patients had no episodes of pancreas-graftrejection. All but one patient had preproliferative or proliferativeretinopathy at base line and had received laser photocoagulationtherapy, which made study of the effects of pancreas transplantationon established lesions of diabetic retinopathy impossible inthese patients. All patients received immunosuppressive treatmentwith prednisone, cyclosporine, and azathioprine throughout the10 years of the study. The study was approved by the Committeefor the Use of Human Subjects in Research of the Universityof Minnesota, and all patients gave written informed consentbefore each evaluation.
Table 1. Demographic Characteristics and Measures of Renal Function at Base Line and 1, 5, and 10 Years after Pancreas Transplantation in Patients with Type 1 Diabetes.
Renal-function tests and metabolic indexes were studied beforepancreas transplantation and 1, 2, 3.5, 5, 7.5, and 10 yearsthereafter. Percutaneous kidney biopsies were performed beforetransplantation and 2, 5, and 10 years thereafter. The resultsof the base-line and five-year follow-up studies of renal structureand function in these patients have been reported elsewhere.15,18We also studied renal structure in biopsy specimens from 66normal subjects who were donating kidneys and who were matchedfor age and sex with the pancreas-transplant recipients. Thesesubjects served as the normal control group for the renal structuralvalues.
Clinical Studies
The patients were hospitalized in the Clinical Research Centerfor one week for assessment before transplantation and for fourto seven days for each follow-up evaluation. The value we usedfor mean blood pressure in each patient was the average of multiplemeasurements of diastolic blood pressure plus one third of thepulse pressure. During each hospitalization, at least three24-hour urine samples were collected for the measurement ofcreatinine clearance and albumin excretion. Serum and urinarycreatinine were measured by the Jaffé reaction; the normalrange for creatinine clearance is 90 to 130 ml per minute per1.73 m2 of body-surface area. Urinary albumin was measured bynephelometry (Beckman Instruments, Fullerton, Calif.); normalvalues are below 22 mg per 24 hours. Glycosylated hemoglobinwas measured by column assay until 1986 and by high-performanceliquid chromatography thereafter (BioRad, Hercules, Calif.)(normal range, 4.0 to 6.1 percent).
Renal-Biopsy Studies
Percutaneous renal biopsies were performed before pancreas transplantationand approximately 5 years (range, 4 to 6) and 10 years (range,9 to 11) after the procedure. The tissue was processed for lightand electron microscopy as previously described.19 Measurementswere made by a single investigator. The base-line and 5-yearbiopsy samples were analyzed earlier than the 10-year samples,but all materials were coded and interspersed with those fromother renal-biopsy studies. Electron-microscopical morphometricanalysis was performed on three to six nonsclerosed glomeruliper biopsy sample (mean, four). The glomeruli were photographedwith a Joel/100 CX electron microscope (Joel, Tokyo, Japan)at a magnification of 3900 in order to obtain photomontagesof the entire glomerular profile for estimation of the mesangialfractional volume (the proportion of the glomerulus occupiedby the mesangium, as previously described).20 Another set ofphotomicrographs (magnification, x12,000) which were producedby entering the glomerulus at its lowest segment and systematicallysampling about 20 percent of the glomerular profile, was usedto measure the thickness of the glomerular basement membrane.21The same photomicrographs were used to measure the fractionof the glomerulus occupied by mesangial matrix (the mesangial-matrixfractional volume) and by mesangial cells (the mesangial-cellfractional volume).4 The thickness of the tubular basement membranewas measured by the orthogonal intercept method on photomicrographs(magnification, x12,000) of proximal segments of the proximaltubules as previously described in detail.6,21 Two to threeblocks of cortical tissue, including 60 to 100 tubular profilesper patient, were studied.
Tissue for light-microscopical analysis was embedded in paraffin,cut into 2-µm sections, and stained with periodic acid–Schiffstain. The mean volume of nonsclerosed glomeruli was estimatedat a magnification of 150 by the method of Weibel and Gomez.22Total mesangial volume, total mesangial-matrix volume, and totalmesangial-cell volume per glomerulus were calculated by multiplyingthe fractional volumes by the mean glomerular volume.
Statistical Analysis
The data are presented as means ±SD, except for the urinaryalbumin excretion rate, for which the median is given. The albuminexcretion rates were not normally distributed and were thereforetransformed logarithmically before analysis. The structuralmeasures in the patients with diabetes at base line and in thenormal subjects were compared with use of Student's unpairedtwo-sided t-test. The values in the patients with diabetes atbase line, 5 years, and 10 years were compared with use of pairedtwo-sided t-tests. Linear regression analyses were performedto test the relations between changes in the albumin excretionrate and changes in structural measures.
Results
The patients' mean glycosylated hemoglobin values were 8.7±1.5percent at base line, 5.3±0.4 percent at 5 years (P<0.001for the comparison with the base-line value), and 5.5±0.7percent at 10 years (P=0.002 for the comparison with the base-linevalue). The mean creatinine clearance rate was lower one yearafter transplantation than at base line and did not change significantlythereafter (Table 1). The median urinary albumin excretion ratedid not change significantly during the study, but the valuesdecreased in all patients who had high base-line values. Themean blood pressure did not change significantly (88±5mm Hg at base line, 92±8 mm Hg 5 years after transplantation[P=0.27 for the comparison with the base-line value], and 97±12mm Hg 10 years after transplantation [P=0.11 for the comparisonwith the base-line value]). Two patients were receiving antihypertensivetherapy at base line, four at 5 years, and four at 10 years.
The mean values for all structural measures were abnormal beforepancreas transplantation (P<0.001 for all comparisons withthe 66 normal subjects) (Figure 1). The thickness of the glomerularbasement membrane did not change significantly from base lineto 5 years, but it had decreased by 10 years (Table 2 and Figure 1).The values at 10 years were normal in four patients andnearly so in the others. Similarly, the thickness of the tubularbasement membrane was substantially unchanged at 5 years andhad decreased significantly by 10 years (Table 2 and Figure 1).
Figure 1. Thickness of the Glomerular Basement Membrane, Thickness of the Tubular Basement Membrane, Mesangial Fractional Volume, and Mesangial-Matrix Fractional Volume at Base Line and 5 and 10 Years after Pancreas Transplantation.
The mesangial fractional volume is the proportion of the glomerulus occupied by the mesangium; the mesangial-matrix fractional volume is the proportion of the glomerulus occupied by mesangial matrix. The shaded areas represent the normal ranges obtained in the 66 age- and sex-matched normal controls (means ±2 SD). Data for individual patients are connected by lines.
Table 2. Measures of Renal Structure at Base Line and 5 and 10 Years after Pancreas Transplantation in Patients with Type 1 Diabetes.
The mesangial fractional volume and the mesangial-matrix fractionalvolume increased from base line to 5 years; at 10 years thesevalues were lower than at base line or at 5 years (Table 2 andFigure 1, respectively). The mesangial-cell fractional volumealso increased from base line to 5 years and then decreasedto the base-line value by 10 years (Table 2).
The mean glomerular volume decreased from base line to 5 yearsand did not change significantly thereafter (Table 2). The productof the mean glomerular volume and the fractional volume providesthe total volume per glomerulus for a given component. The totalmesangial volume per glomerulus and the total mesangial-matrixvolume per glomerulus did not change significantly from baseline to 5 years (P=0.72 and P=0.87, respectively); both weresignificantly lower at 10 years than at base line (P=0.01 forboth) and at 5 years (P=0.02 for both; data not shown). Totalmesangial-cell volume per glomerulus did not change from baseline to 5 years (P=0.52) but was lower at 10 years than at baseline (P=0.06) or at 5 years (P=0.05; data not shown). The changein the urinary albumin excretion rate from base line to 10 yearsafter transplantation was correlated with the change in mesangialfractional volume over that period (r=0.73, P=0.04) but notwith the change in any other structural measure.
Photomicrographs of glomeruli that typify those present in eachof the biopsy specimens from two patients illustrate the potentialfor diabetic glomerular lesions to be reversed. The first patienthad diffuse mesangial expansion and Kimmelstiel–Wilsonnodules at base line (Figure 2A). Mesangial expansion was stillevident at 5 years (Figure 2B) but had nearly completely disappeared10 years after pancreas transplantation (Figure 2C). The secondpatient had milder diffuse mesangial expansion at base line(Figure 3A); mesangial expansion was slightly increased at 5years (Figure 3B), whereas at 10 years glomerular structurewas nearly normal (Figure 3C).
Figure 2. Photomicrographs of Renal-Biopsy Specimens Obtained before and after Pancreas Transplantation from a 33-Year-Old Woman with Type 1 Diabetes of 17 Years' Duration at the Time of Transplantation (Periodic Acid–Schiff, x120).
Panel A shows a typical glomerulus from the base-line biopsy specimen, which is characterized by diffuse and nodular (Kimmelstiel–Wilson) diabetic glomerulopathy. Mesangial-matrix expansion and the palisading of mesangial nuclei around the nodular lesions are evident. In Panel B, a typical glomerulus five years after transplantation shows the persistence of the diffuse and nodular lesions. Panel C shows a typical glomerulus 10 years after transplantation, with marked resolution of diffuse and nodular mesangial lesions and more open glomerular capillary lumina.
Figure 3. Photomicrographs of Renal-Biopsy Specimens Obtained before and after Pancreas Transplantation from a 31-Year-Old Woman with Type 1 Diabetes of 27 Years' Duration at the Time of Transplantation (Periodic Acid–Schiff, x120).
Panel A shows a typical glomerulus from the base-line biopsy specimen, characterized by mild, diffuse diabetic mesangial expansion. Panel B shows a typical glomerulus five years after pancreas transplantation, in which the persistence of the diffuse mesangial expansion is evident. In Panel C, a typical glomerulus 10 years after transplantation shows the reversion to nearly normal glomerular architecture.
Discussion
We found that 10 years of normoglycemia after pancreas transplantationameliorated the glomerular and tubular lesions that characterizediabetic nephropathy in patients with long-term type 1 diabeteswho have not received renal grafts. The beneficial effects ofpancreas transplantation, including reductions in the thicknessof the glomerular and tubular basement membranes and in mesangialmatrix, as well as the disappearance of Kimmelstiel–Wilsonnodular lesions, represent substantial remodeling of the glomerulararchitecture. That it took many years for the lesions to bereversed is consistent with their slow development.3,8,20 Infact, diabetic renal lesions develop and progress for at leasta decade after the onset of diabetes before they cause any functionalabnormalities in the subgroup of diabetic patients in whom clinicalnephropathy eventually develops.20 Most patients with type 1diabetes, however, never have clinical renal disease,23 andin these patients the structure of the kidney remains normalfor many years, after which mild diabetic changes may very slowlybecome discernible.8,20 Urinary albumin excretion rates largelyparallel these structural changes, remaining normal in manypatients,20 with microalbuminuria20 and proteinuria3 typicallyreflecting the presence of moderate and advanced lesions, respectively.
The improvement in glomerular structure in our patients 10 yearsafter pancreas transplantation contrasts sharply with the lackof change in these patients 5 years after transplantation andalso with the stable glomerular-basement-membrane thicknessand increasing total and fractional mesangial volumes in a similargroup of 11 patients with diabetes in whom renal biopsies wereperformed at intervals of 5 years.15,24 Sequential biopsiesin renal-transplant recipients with diabetes also showed progressionand no evidence of spontaneous reversal of diabetic glomerularlesions over time.9,12,25
The current results cannot be explained by the patients' immunosuppressivetherapy. In patients with diabetes who have received renal allografts,nephropathic lesions develop at rates similar to those in diabeticpatients with their own kidneys,25,26 despite immunosuppressivetherapy. Furthermore, the rates of development of lesions inpatients with diabetes who have received renal allografts aresimilar in those who receive cyclosporine after transplantationand those who do not (unpublished data). Thus, the improvementin kidney structure in the patients described here was mostlikely due to prolonged normoglycemia.
The reasons for the time necessary for the reversal of the lesionsof diabetic nephropathy are unknown. The main change in renalstructure in diabetes is the accumulation of extracellular matrix,which in our patients was reduced at 10 years after pancreastransplantation but not at 5 years. One possibility is thatextracellular-matrix molecules are heavily glycosylated andcross-linked as a consequence of long-standing hyperglycemia,rendering them relatively unsusceptible to degradation.27,28Perhaps as glycosylated matrix is slowly replaced by less glycosylatedmolecules, degradation of the accumulated matrix becomes possible.It is also conceivable that hyperglycemia induces phenotypicalterations in renal cells that persist despite the return ofnormoglycemia (the so-called memory effect).29,30
Patients with type 1 diabetes can have well-established lesionsof diabetic nephropathy but normal urinary albumin excretionrates, glomerular filtration rates, and blood pressure,20 aswas the case in some of our patients. Moreover, increasing urinaryalbumin excretion, from initial normoalbuminuria to microalbuminuriaor from microalbuminuria to overt nephropathy, has been relatedto progressive mesangial expansion2,3,5,20,24 and may occurin the absence of further thickening of the glomerular basementmembrane or interstitial expansion.24 The patients' median urinaryalbumin excretion rate did not change significantly after pancreastransplantation, but the values decreased in all patients inwhom the rate had been elevated at base line. Furthermore, thechange in the albumin excretion rate correlated with the changein mesangial fractional volume during the 10 years of this study.Thus, the reversibility of mesangial expansion in patients withdiabetes may have important functional implications. The changesin creatinine clearance were confounded by the effects of cyclosporineon the glomerular filtration rate; in fact, the dose of cyclosporineand the degree of the early decline in creatinine clearancewere closely related in these patients.18 Nonetheless, afterthe initial reduction in the creatinine clearance rate at oneyear, the rate was stable.
We conclude that glomerular lesions characteristic of diabetes,including Kimmelstiel–Wilson nodules, as well as tubularlesions, are reversible in patients with type 1 diabetes duringlong-term normoglycemia achieved by pancreas transplantation.The beneficial effects must be considered along with the nephrotoxiceffects of some current immunosuppressive agents, especiallycyclosporine,18,31,32 the risks of surgery, and the adverseconsequences of lifelong immunosuppression. The achievementof normoglycemia by means of improved immunomodulation, islettransplantation, or other methods offers hope of reversing diabeticrenal injury with less risk than today's technology allows.
Supported by grants from the National Institutes of Health (DK13083and DK43605), the National Center for Research Resources (MO1-KK00400),and the Juvenile Diabetes Foundation International. Dr. Fiorettois the recipient of a Juvenile Diabetes Foundation InternationalCareer Development Award.
We are indebted to the patients who participated in these studiesand who, over more than a decade, have cooperated with the demandingresearch protocols; to Ms. Susan Sisson-Ross and Mr. John Basgenfor their excellent technical assistance; and to Ms. PatriciaErickson and Ms. Sandra Cragg for secretarial assistance.
Source Information
From the Department of Internal Medicine and the Center for the Study of Aging of the National Research Council, University of Padua Medical School, Padua, Italy (P.F.); and the Departments of Laboratory Medicine and Pathology (M.W.S.), Surgery (D.E.R.S.), Medicine (F.C.G.), and Pediatrics (M.M.), University of Minnesota School of Medicine, Minneapolis.
Address reprint requests to Dr. Mauer at the Department of Pediatrics, University of Minnesota, Box 491, UMHC, 420 Delaware St. S.E., Minneapolis, MN 55455-0392, or Dr. Fioretto at the Department of Internal Medicine, University of Padua, Via Giustiani, No. 2, Padua 35128, Italy.
References
Incidence and causes of treated ESRD. Am J Kidney Dis 1994;24:Suppl2:S48-S56.
Steffes MW, Østerby R, Chavers B, Mauer SM. Mesangial expansion as a central mechanism for loss of kidney function in diabetic patients. Diabetes 1989;38:1077-1081. [Abstract]
Mauer SM, Steffes MW, Ellis EN, Sutherland DER, Brown DM, Goetz FC. Structural-functional relationships in diabetic nephropathy. J Clin Invest 1984;74:1143-1155.
Steffes MW, Bilous RW, Sutherland DER, Mauer SM. Cell and matrix components of the glomerular mesangium in type I diabetes. Diabetes 1992;41:679-684. [Abstract]
Fioretto P, Steffes MW, Brown DM, Mauer SM. An overview of renal pathology in insulin-dependent diabetes mellitus in relationship to altered glomerular hemodynamics. Am J Kidney Dis 1992;20:549-558. [Medline]
Brito PL, Fioretto P, Drummond K, et al. Proximal tubular basement membrane width in insulin-dependent diabetes mellitus. Kidney Int 1998;53:754-761. [CrossRef][Medline]
Pirart J. Diabetes mellitus and its degenerative complications: a prospective study of 4,400 patients observed between 1947 and 1973. Diabetes Care 1978;1:168-88, 252.
Steffes MW, Sutherland DER, Goetz FC, Rich SS, Mauer SM. Studies of kidney and muscle biopsy specimens from identical twins discordant for Type I diabetes mellitus. N Engl J Med 1985;312:1282-1287. [Abstract]
Mauer SM, Steffes MW, Connett J, Najarian JS, Sutherland DER, Barbosa J. The development of lesions in the glomerular basement membrane and mesangium after transplantation of normal kidneys to diabetic patients. Diabetes 1983;32:948-952. [Abstract]
Østerby R, Nyberg G, Hedman L, Karlberg I, Persson H, Svalander C. Kidney transplantation in type 1 (insulin-dependent) diabetic patients: early glomerulopathy. Diabetologia 1991;34:668-674. [CrossRef][Medline]
The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. N Engl J Med 1993;329:977-986. [Free Full Text]
Barbosa J, Steffes MW, Sutherland DE, Connett J, Rao KV, Mauer SM. Effects of glycemic control on early diabetic renal lesions: a 5-year randomized controlled clinical trial of insulin-dependent diabetic kidney transplant recipients. JAMA 1994;272:600-606. [Abstract]
Bangstad HJ, Østerby R, Dahl-Jørgensen K, Berg KJ, Hartmann A, Hanssen KF. Improvement of blood glucose control in IDDM patients retards the progression of morphological changes in early diabetic nephropathy. Diabetologia 1994;37:483-490. [CrossRef][Medline]
Bilous RW, Mauer SM, Sutherland DER, Najarian JS, Goetz FC, Steffes MW. The effects of pancreas transplantation on the glomerular structure of renal allografts in patients with insulin-dependent diabetes. N Engl J Med 1989;321:80-85. [Abstract]
Fioretto P, Mauer SM, Bilous RW, Goetz FC, Sutherland DER, Steffes MW. Effects of pancreas transplantation on glomerular structure in insulin-dependent diabetic patients with their own kidneys. Lancet 1993;342:1193-1196. [CrossRef][Medline]
Sutherland DER, Gores PF, Farney AC, et al. Evolution of kidney, pancreas, and islet transplantation for patients with diabetes at the University of Minnesota. Am J Surg 1993;166:456-491. [CrossRef][Medline]
Sutherland DER. Present status of pancreas transplantation alone in nonuremic diabetic patients. Transplant Proc 1994;26:379-383. [Medline]
Fioretto P, Steffes MW, Mihatsch MJ, Strøm EH, Sutherland DER, Mauer M. Cyclosporine associated lesions in native kidneys of diabetic pancreas transplant recipients. Kidney Int 1995;48:489-495. [Medline]
Ellis EN, Basgen JM, Mauer SM, Steffes MW. Kidney biopsy technique and evaluation. In: Clarke WL, Larner J, Pohl SL, eds. Methods in diabetes research. Vol. 2. Clinical methods. New York: John Wiley, 1986:633-47.
Fioretto P, Steffes MW, Mauer M. Glomerular structure in nonproteinuric IDDM patients with various levels of albuminuria. Diabetes 1994;43:1358-1364. [Abstract]
Jensen EB, Gundersen HJG, Østerby R. Determination of membrane thickness distribution from orthogonal intercepts. J Microsc 1979;115:19-33. [Medline]
Weibel ER, Gomez DM. A principle for counting tissue structures on random sections. J Appl Physiol 1962;17:343-348. [Free Full Text]
Krolewski AS, Warram JH, Christlieb AR, Busick EJ, Kahn CR. The changing natural history of nephropathy in type I diabetes. Am J Med 1985;78:785-794. [CrossRef][Medline]
Fioretto P, Steffes MW, Sutherland DER, Mauer M. Sequential renal biopsies in insulin-dependent diabetic patients: structural factors associated with clinical progression. Kidney Int 1995;48:1929-1935. [Medline]
Mauer SM, Goetz FC, McHugh LE, et al. Long-term study of normal kidneys transplanted into patients with type I diabetes. Diabetes 1989;38:516-523. [Abstract]
Moriya R, Steffes M, Mauer M. Does having one kidney accelerate the development of diabetic nephropathy (DN) lesions in patients with insulin-dependent diabetes mellitus (IDDM)? J Am Soc Nephrol 1996;7:1362-1362.abstract
Brownlee M, Cerami A, Vlassara H. Advanced glycosylation end products in tissue and the biochemical basis of diabetic complications. N Engl J Med 1988;318:1315-1321. [Medline]
Lubec G, Pollack A. Reduced susceptibility of nonenzymatically glucosylated glomerular basement membrane to proteases: is thickening of diabetic glomerular basement membranes due to reduced proteolytic degradation? Renal Physiol 1980;3:4-8. [Medline]
Roy S, Sala R, Cagliero E, Lorenzi M. Overexpression of fibronectin induced by diabetes or high glucose: phenomenon with a memory. Proc Natl Acad Sci U S A 1990;87:404-408. [Free Full Text]
Mecham RP, Whitehouse LA, Wrenn DS, et al. Smooth muscle-mediated connective tissue remodeling in pulmonary hypertension. Science 1987;237:423-426. [Free Full Text]
Myers BD, Sibley R, Newton L, et al. The long-term course of cyclosporine-associated chronic nephropathy. Kidney Int 1988;33:590-600. [Medline]
Feutren G, Mihatsch MJ. Risk factors for cyclosporine-induced nephropathy in patients with autoimmune diseases. N Engl J Med 1992;326:1654-1660. [Abstract]
Boucek, P., Havrdova, T., Voska, L., Lodererova, A., He, L., Saudek, F., Lipar, K., Adamec, M., Sommer, C.
(2008). Epidermal Innervation in Type 1 Diabetic Patients: A 2.5-year prospective study after simultaneous pancreas/kidney transplantation. Diabetes Care
31: 1611-1612
[Abstract][Full Text]
Morath, C., Zeier, M., Dohler, B., Schmidt, J., Nawroth, P. P., Opelz, G.
(2008). Metabolic Control Improves Long-Term Renal Allograft and Patient Survival in Type 1 Diabetes. J. Am. Soc. Nephrol.
19: 1557-1563
[Abstract][Full Text]
Piecha, G., Koleganova, N., Gross, M.-L., Geldyyev, A., Adamczak, M., Ritz, E.
(2008). Regression of glomerulosclerosis in subtotally nephrectomized rats: effects of monotherapy with losartan, spironolactone, and their combination. Am. J. Physiol. Renal Physiol.
295: F137-F144
[Abstract][Full Text]
Ruggenenti, P., Perticucci, E., Cravedi, P., Gambara, V., Costantini, M., Sharma, S. K., Perna, A., Remuzzi, G.
(2008). Role of Remission Clinics in the Longitudinal Treatment of CKD. J. Am. Soc. Nephrol.
19: 1213-1224
[Full Text]
Frystyk, J., Ritzel, R. A., Maubach, J., Busing, M., Luck, R., Klempnauer, J., Schmiegel, W., Nauck, M. A.
(2008). Comparison of Pancreas-Transplanted Type 1 Diabetic Patients with Portal-Venous Versus Systemic-Venous Graft Drainage: Impact on Glucose Regulatory Hormones and the Growth Hormone/Insulin-Like Growth Factor-I Axis. J. Clin. Endocrinol. Metab.
93: 1758-1766
[Abstract][Full Text]
Bloomgarden, Z. T.
(2008). Diabetic Nephropathy. Diabetes Care
31: 823-827
[Abstract][Full Text]
Barbey, F., Lidove, O., Schwarting, A.
(2008). Fabry nephropathy: 5 years of enzyme replacement therapy--a short review. NDT Plus
1: 11-19
[Full Text]
Nakagawa, T., Segal, M., Croker, B., Johnson, R. J.
(2007). A breakthrough in diabetic nephropathy: the role of endothelial dysfunction. Nephrol Dial Transplant
22: 2775-2777
[Full Text]
Mehra, S., Tavakoli, M., Kallinikos, P. A., Efron, N., Boulton, A. J.M., Augustine, T., Malik, R. A.
(2007). Corneal Confocal Microscopy Detects Early Nerve Regeneration After Pancreas Transplantation in Patients With Type 1 Diabetes. Diabetes Care
30: 2608-2612
[Abstract][Full Text]
Maffi, P., Bertuzzi, F., De Taddeo, F., Magistretti, P., Nano, R., Fiorina, P., Caumo, A., Pozzi, P., Socci, C., Venturini, M., del Maschio, A., Secchi, A.
(2007). Kidney Function After Islet Transplant Alone in Type 1 Diabetes: Impact of immunosuppressive therapy on progression of diabetic nephropathy. Diabetes Care
30: 1150-1155
[Abstract][Full Text]
Fiorina, P., Perseghin, G., De Cobelli, F., Gremizzi, C., Petrelli, A., Monti, L., Maffi, P., Luzi, L., Secchi, A., Del Maschio, A.
(2007). Altered Kidney Graft High-Energy Phosphate Metabolism in Kidney-Transplanted End-Stage Renal Disease Type 1 Diabetic Patients: A cross-sectional analysis of the effect of kidney alone and kidney-pancreas transplantation. Diabetes Care
30: 597-603
[Abstract][Full Text]
Eddy, A. A., Fogo, A. B.
(2006). Plasminogen Activator Inhibitor-1 in Chronic Kidney Disease: Evidence and Mechanisms of Action. J. Am. Soc. Nephrol.
17: 2999-3012
[Full Text]
Liang, X.-B., Ma, L.-J., Naito, T., Wang, Y., Madaio, M., Zent, R., Pozzi, A., Fogo, A. B.
(2006). Angiotensin Type 1 Receptor Blocker Restores Podocyte Potential to Promote Glomerular Endothelial Cell Growth. J. Am. Soc. Nephrol.
17: 1886-1895
[Abstract][Full Text]
Lloberas, N., Cruzado, J. M., Franquesa, M., Herrero-Fresneda, I., Torras, J., Alperovich, G., Rama, I., Vidal, A., Grinyo, J. M.
(2006). Mammalian Target of Rapamycin Pathway Blockade Slows Progression of Diabetic Kidney Disease in Rats. J. Am. Soc. Nephrol.
17: 1395-1404
[Abstract][Full Text]
Placier, S., Boffa, J.-J., Dussaule, J.-C., Chatziantoniou, C.
(2006). Reversal of renal lesions following interruption of nitric oxide synthesis inhibition in transgenic mice. Nephrol Dial Transplant
21: 881-888
[Abstract][Full Text]
Piccoli, G. B., Sargiotto, A., Burdese, M., Consiglio, V., Mezza, E., Rossetti, M., Picciotto, G., Segoloni, G. P.
(2006). Grafted kidney, native kidney and proteinuria after pre-emptive pancreas-kidney transplantation: questions and answers. Nephrol Dial Transplant
21: 1139-1140
[Full Text]
Al-Rasheed, N. M., Willars, G. B., Brunskill, N. J.
(2006). C-Peptide Signals via G{alpha}i to Protect against TNF-{alpha}-Mediated Apoptosis of Opossum Kidney Proximal Tubular Cells. J. Am. Soc. Nephrol.
17: 986-995
[Abstract][Full Text]
Fioretto, P., Bruseghin, M., Berto, I., Gallina, P., Manzato, E., Mussap, M.
(2006). Renal Protection in Diabetes: Role of Glycemic Control. J. Am. Soc. Nephrol.
17: S86-S89
[Abstract][Full Text]
Lu, Y., Wang, Z., Zhu, M.
(2006). Human bone marrow mesenchymal stem cells transfected with human insulin genes can secrete insulin stably.. Annals of Clinical & Laboratory Science
36: 127-136
[Abstract][Full Text]
Fujihara, C. K., Sena, C. R., Malheiros, D. M. A. C., Mattar, A. L., Zatz, R.
(2006). Short-term nitric oxide inhibition induces progressive nephropathy after regression of initial renal injury. Am. J. Physiol. Renal Physiol.
290: F632-F640
[Abstract][Full Text]
Fogo, A. B.
(2006). Progression versus regression of chronic kidney disease. Nephrol Dial Transplant
21: 281-284
[Full Text]
Eikmans, M., Aben, J. A., Koop, K., Baelde, H. J., de Heer, E., Bruijn, J. A.
(2006). Genetic factors in progressive renal disease: the good ones, the bad ones and the ugly ducklings. Nephrol Dial Transplant
21: 257-260
[Full Text]
Hall, P. M.
(2006). Prevention of Progression in Diabetic Nephropathy. Diabetes Spectr.
19: 18-24
[Abstract][Full Text]
Kosugi, T., Yuzawa, Y., Sato, W., Kawai, H., Matsuo, S., Takei, Y., Muramatsu, T., Kadomatsu, K.
(2006). Growth Factor Midkine Is Involved in the Pathogenesis of Diabetic Nephropathy. Am. J. Pathol.
168: 9-19
[Abstract][Full Text]
Yamada, T., Komatsu, M., Komiya, I., Miyahara, Y., Shima, Y., Matsuzaki, M., Ishikawa, Y., Mita, R., Fujiwara, M., Furusato, N., Nishi, K., Aizawa, T.
(2005). Development, Progression, and Regression of Microalbuminuria in Japanese Patients With Type 2 Diabetes Under Tight Glycemic and Blood Pressure Control: The Kashiwa Study. Diabetes Care
28: 2733-2738
[Abstract][Full Text]
Aldigier, J. C., Kanjanbuch, T., Ma, L.-J., Brown, N. J., Fogo, A. B.
(2005). Regression of Existing Glomerulosclerosis by Inhibition of Aldosterone. J. Am. Soc. Nephrol.
16: 3306-3314
[Abstract][Full Text]
Fiorina, P., Venturini, M., Folli, F., Losio, C., Maffi, P., Placidi, C., La Rosa, S., Orsenigo, E., Socci, C., Capella, C., Del Maschio, A., Secchi, A.
(2005). Natural History of Kidney Graft Survival, Hypertrophy, and Vascular Function in End-Stage Renal Disease Type 1 Diabetic Kidney-Transplanted Patients: Beneficial impact of pancreas and successful islet cotransplantation. Diabetes Care
28: 1303-1310
[Abstract][Full Text]
Coppelli, A., Giannarelli, R., Vistoli, F., Del Prato, S., Rizzo, G., Mosca, F., Boggi, U., Marchetti, P.
(2005). The Beneficial Effects of Pancreas Transplant Alone on Diabetic Nephropathy. Diabetes Care
28: 1366-1370
[Abstract][Full Text]
Ma, L.-J., Nakamura, S., Aldigier, J. C., Rossini, M., Yang, H., Liang, X., Nakamura, I., Marcantoni, C., Fogo, A. B.
(2005). Regression of Glomerulosclerosis with High-Dose Angiotensin Inhibition Is Linked to Decreased Plasminogen Activator Inhibitor-1. J. Am. Soc. Nephrol.
16: 966-976
[Abstract][Full Text]
Remuzzi, G., Remuzzi, A.
(2005). Is Regression of Chronic Nephropathies a Therapeutic Target?. J. Am. Soc. Nephrol.
16: 840-842
[Full Text]
Samnegard, B., Jacobson, S. H., Jaremko, G., Johansson, B.-L., Ekberg, K., Isaksson, B., Eriksson, L., Wahren, J., Sjoquist, M.
(2005). C-peptide prevents glomerular hypertrophy and mesangial matrix expansion in diabetic rats. Nephrol Dial Transplant
20: 532-538
[Abstract][Full Text]
Fioretto, P., Solini, A.
(2005). Antihypertensive Treatment and Multifactorial Approach for Renal Protection in Diabetes. J. Am. Soc. Nephrol.
16: S18-S21
[Abstract][Full Text]
Venturini, M., Angeli, E., Maffi, P., Fiorina, P., Bertuzzi, F., Salvioni, M., De Cobelli, F., Socci, C., Aldrighetti, L., Losio, C., Di Carlo, V., Secchi, A., Del Maschio, A.
(2005). Technique, Complications, and Therapeutic Efficacy of Percutaneous Transplantation of Human Pancreatic Islet Cells in Type 1 Diabetes: The Role of US. Radiology
234: 617-624
[Abstract][Full Text]
Maestroni, A., Ruggieri, D., Dell'Antonio, G., Luzi, L., Zerbini, G.
(2005). C-peptide increases the expression of vasopressin-activated calcium-mobilizing receptor gene through a G protein-dependent pathway. Eur J Endocrinol
152: 135-141
[Abstract][Full Text]
Gross, J. L., de Azevedo, M. J., Silveiro, S. P., Canani, L. H., Caramori, M. L., Zelmanovitz, T.
(2005). Diabetic Nephropathy: Diagnosis, Prevention, and Treatment. Diabetes Care
28: 164-176
[Abstract][Full Text]
Larsen, J. L.
(2004). Pancreas Transplantation: Indications and Consequences. Endocr. Rev.
25: 919-946
[Abstract][Full Text]
Adamczak, M., Gross, M.-L., Amann, K., Ritz, E.
(2004). Reversal of Glomerular Lesions Involves Coordinated Restructuring of Glomerular Microvasculature. J. Am. Soc. Nephrol.
15: 3063-3072
[Abstract][Full Text]
Larsen, J. L., Colling, C. W., Ratanasuwan, T., Burkman, T. W., Lynch, T. G., Erickson, J. M., Lyden, E. R., Lane, J. T., Mack-Shipman, L. R.
(2004). Pancreas Transplantation Improves Vascular Disease in Patients With Type 1 Diabetes. Diabetes Care
27: 1706-1711
[Abstract][Full Text]
Bloomgarden, Z. T.
(2004). Diabetes Complications. Diabetes Care
27: 1506-1514
[Full Text]
Hovind, P., Tarnow, L., Rossing, P., Jensen, B. R., Graae, M., Torp, I., Binder, C., Parving, H.-H.
(2004). Predictors for the development of microalbuminuria and macroalbuminuria in patients with type 1 diabetes: inception cohort study. BMJ
328: 1105-
[Abstract][Full Text]
De Cobelli, F., Fiorina, P., Perseghin, G., Magnone, M., Venturini, M., Zerbini, G., Zanello, A., Mazzolari, G., Monti, L., Di Carlo, V., Secchi, A., Del Maschio, A.
(2004). L-Arginine-Induced Vasodilation of the Renal Vasculature Is Preserved in Uremic Type 1 Diabetic Patients After Kidney and Pancreas but not After Kidney-Alone Transplantation. Diabetes Care
27: 947-954
[Abstract][Full Text]
Hertig, A., Rondeau, E.
(2004). Role of the Coagulation/Fibrinolysis System in Fibrin-Associated Glomerular Injury. J. Am. Soc. Nephrol.
15: 844-853
[Abstract][Full Text]
Robertson, R. P.
(2004). Islet Transplantation as a Treatment for Diabetes -- A Work in Progress. NEJM
350: 694-705
[Full Text]
Venstrom, J. M., McBride, M. A., Rother, K. I., Hirshberg, B., Orchard, T. J., Harlan, D. M.
(2003). Survival After Pancreas Transplantation in Patients With Diabetes and Preserved Kidney Function. JAMA
290: 2817-2823
[Abstract][Full Text]
Nathan, D. M.
(2003). Isolated Pancreas Transplantation for Type 1 Diabetes: A Doctor's Dilemma. JAMA
290: 2861-2863
[Full Text]
Adamczak, M., Gross, M.-L., Krtil, J., Koch, A., Tyralla, K., Amann, K., Ritz, E.
(2003). Reversal of Glomerulosclerosis after High-Dose Enalapril Treatment in Subtotally Nephrectomized Rats. J. Am. Soc. Nephrol.
14: 2833-2842
[Abstract][Full Text]
Fogo, A. B.
(2003). Regression Lines in Chronic Kidney Disease. J. Am. Soc. Nephrol.
14: 2990-2991
[Full Text]
Torffvit, O.
(2003). Hyperglycaemia in diabetes: impact on nephropathy and cardiac risk. Nephrol Dial Transplant
18: 1711-1715
[Full Text]
Locatelli, F., Canaud, B., Eckardt, K.-U., Stenvinkel, P., Wanner, C., Zoccali, C.
(2003). The importance of diabetic nephropathy in current nephrological practice. Nephrol Dial Transplant
18: 1716-1725
[Abstract][Full Text]
Fiorina, P., Folli, F., Zerbini, G., Maffi, P., Gremizzi, C., Di Carlo, V., Socci, C., Bertuzzi, F., Kashgarian, M., Secchi, A.
(2003). Islet Transplantation Is Associated with Improvement of Renal Function among Uremic Patients with Type I Diabetes Mellitus and Kidney Transplants. J. Am. Soc. Nephrol.
14: 2150-2158
[Abstract][Full Text]
Shapiro, A. M. J.
(2003). Islet Transplants and Impact on Secondary Diabetic Complications: Does C-Peptide Protect the Kidney?. J. Am. Soc. Nephrol.
14: 2214-2216
[Full Text]
Ha, H., Lee, H. B.
(2003). Reactive Oxygen Species and Matrix Remodeling in Diabetic Kidney. J. Am. Soc. Nephrol.
14: S246-249
[Abstract][Full Text]
Drummond, K. N., Kramer, M. S., Suissa, S., Levy-Marchal, C., Dell'Aniello, S., Sinaiko, A., Mauer, M.
(2003). Effects of Duration and Age at Onset of Type 1 Diabetes on Preclinical Manifestations of Nephropathy. Diabetes
52: 1818-1824
[Abstract][Full Text]
Chadban, S. J., Briganti, E. M., Kerr, P. G., Dunstan, D. W., Welborn, T. A., Zimmet, P. Z., Atkins, R. C.
(2003). Prevalence of Kidney Damage in Australian Adults: The AusDiab Kidney Study. J. Am. Soc. Nephrol.
14: S131-138
[Abstract][Full Text]
Yu, H. T.
(2003). Progression of Chronic Renal Failure. Arch Intern Med
163: 1417-1429
[Abstract][Full Text]
Ritz, E.
(2003). Albuminuria and Vascular Damage -- The Vicious Twins. NEJM
348: 2349-2352
[Full Text]
Boffa, J.-J., Lu, Y., Placier, S., Stefanski, A., Dussaule, J.-C., Chatziantoniou, C.
(2003). Regression of Renal Vascular and Glomerular Fibrosis: Role of Angiotensin II Receptor Antagonism and Matrix Metalloproteinases. J. Am. Soc. Nephrol.
14: 1132-1144
[Abstract][Full Text]
Sawai, K., Mori, K., Mukoyama, M., Sugawara, A., Suganami, T., Koshikawa, M., Yahata, K., Makino, H., Nagae, T., Fujinaga, Y., Yokoi, H., Yoshioka, T., Yoshimoto, A., Tanaka, I., Nakao, K.
(2003). Angiogenic Protein Cyr61 is Expressed by Podocytes in Anti-Thy-1 Glomerulonephritis. J. Am. Soc. Nephrol.
14: 1154-1163
[Abstract][Full Text]
Haneda, M., Koya, D., Isono, M., Kikkawa, R.
(2003). Overview of Glucose Signaling in Mesangial Cells in Diabetic Nephropathy. J. Am. Soc. Nephrol.
14: 1374-1382
[Full Text]
Wolf, G., Ritz, E.
(2003). Diabetic Nephropathy in Type 2 Diabetes Prevention and Patient Management. J. Am. Soc. Nephrol.
14: 1396-1405
[Full Text]
Abbate, M., Remuzzi, G.
(2003). Can We Really Lessen Kidney Damage to the Point that the Loss of Renal Function of Progressive Nephropathy May Revert?. J. Am. Soc. Nephrol.
14: 1411-1414
[Full Text]
Loon, N. R.
(2003). Diabetic Kidney Disease: Preventing Dialysis and Transplantation. Clin. Diabetes
21: 55-62
[Abstract][Full Text]
Kelly, D. J., Zhang, Y., Hepper, C., Gow, R. M., Jaworski, K., Kemp, B. E., Wilkinson-Berka, J. L., Gilbert, R. E.
(2003). Protein Kinase C {beta} Inhibition Attenuates the Progression of Experimental Diabetic Nephropathy in the Presence of Continued Hypertension. Diabetes
52: 512-518
[Abstract][Full Text]
Mauer, M., Zinman, B., Gardiner, R., Drummond, K. N, Suissa, S., Donnelly, S. M, Strand, T. D, Kramer, M. S, Klein, R., Sinaiko, A. R
(2002). ACE-I and ARBs in early diabetic nephropathy. Journal of Renin-Angiotensin-Aldosterone System
3: 262-269
[Abstract]
Mishra, R., Leahy, P., Simonson, M. S.
(2002). Gene expression profiling reveals role for EGF-family ligands in mesangial cell proliferation. Am. J. Physiol. Renal Physiol.
283: F1151-F1159
[Abstract][Full Text]
Eddy, A. A.
(2002). Plasminogen activator inhibitor-1 and the kidney. Am. J. Physiol. Renal Physiol.
283: F209-F220
[Abstract][Full Text]
Makino, H., Tanaka, I., Mukoyama, M., Sugawara, A., Mori, K., Muro, S., Suganami, T., Yahata, K., Ishibashi, R., Ohuchida, S., Maruyama, T., Narumiya, S., Nakao, K.
(2002). Prevention of Diabetic Nephropathy in Rats by Prostaglandin E Receptor EP1-Selective Antagonist. J. Am. Soc. Nephrol.
13: 1757-1765
[Abstract][Full Text]
Houlihan, C. A., Akdeniz, A., Tsalamandris, C., Cooper, M. E., Jerums, G., Gilbert, R. E.
(2002). Urinary Transforming Growth Factor-{beta} Excretion in Patients With Hypertension, Type 2 Diabetes, and Elevated Albumin Excretion Rate: Effects of angiotensin receptor blockade and sodium restriction. Diabetes Care
25: 1072-1077
[Abstract][Full Text]
Rerolle, J. P., Thervet, E., Anglicheau, D., Desgrandchamps, F., Nochy, D., Janin, A., Fornairon, S., Passa, P., Bedrossian, J., Legendre, C.
(2002). Long-term renal allograft outcome after simultaneous kidney and pancreas transplantation. Nephrol Dial Transplant
17: 905-909
[Abstract][Full Text]
Hariharan, S., Pirsch, J. D., Lu, C. Y., Chan, L., Pesavento, T. E., Alexander, S., Bumgardner, G. L., Baasadona, G., Hricik, D. E., Pescovitz, M. D., Rubin, N. T., Stratta, R. J.
(2002). Pancreas after Kidney Transplantation. J. Am. Soc. Nephrol.
13: 1109-1118
[Full Text]
Shokouh-Amiri, M. H., Stratta, R. J., Latif, K. A., Gaber, O.
(2002). Glucose Control During and After Pancreatic Transplantation. Diabetes Spectr.
15: 49-53
[Abstract][Full Text]
Kurokawa, K., Nangaku, M., Saito, A., Inagi, R., Miyata, T.
(2002). Current Issues and Future Perspectives of Chronic Renal Failure. J. Am. Soc. Nephrol.
13: S3-6
[Full Text]
Hovind, P., Rossing, P., Tarnow, L., Toft, H., Parving, J., Parving, H.-H.
(2001). Remission of Nephrotic-Range Albuminuria in Type 1 Diabetic Patients. Diabetes Care
24: 1972-1977
[Abstract][Full Text]
GRUESSNER, A. C., SUTHERLAND, D. E. R., DUNN, D. L., NAJARIAN, J. S., HUMAR, A., KANDASWAMY, R., GRUESSNER, R. W. G.
(2001). Pancreas after Kidney Transplants in Posturemic Patients with Type I Diabetes Mellitus. J. Am. Soc. Nephrol.
12: 2490-2499
[Abstract][Full Text]
BECKER, B. N., ODORICO, J. S., BECKER, Y. T., GROSHEK, M., WERWINSKI, C., PIRSCH, J. D., SOLLINGER, H. W.
(2001). Simultaneous Pancreas-Kidney and Pancreas Transplantation. J. Am. Soc. Nephrol.
12: 2517-2527
[Full Text]
Thomas, M. C., Mathew, T. H., Russ, G. R.
(2001). Glycaemic control and graft loss following renal transplantation. Nephrol Dial Transplant
16: 1978-1982
[Full Text]
Assady, S., Maor, G., Amit, M., Itskovitz-Eldor, J., Skorecki, K. L., Tzukerman, M.
(2001). Insulin Production by Human Embryonic Stem Cells. Diabetes
50: 1691-1697
[Abstract][Full Text]
Krishnamurti, U., Steffes, M. W.
(2001). Glycohemoglobin: A Primary Predictor of the Development or Reversal of Complications of Diabetes Mellitus. Clin. Chem.
47: 1157-1165
[Abstract][Full Text]
Schiffmann, R., Kopp, J. B., Austin III, H. A., Sabnis, S., Moore, D. F., Weibel, T., Balow, J. E., Brady, R. O.
(2001). Enzyme Replacement Therapy in Fabry Disease: A Randomized Controlled Trial. JAMA
285: 2743-2749
[Abstract][Full Text]
White, S A, Kimber, R, Veitch, P S, Nicholson, M L
(2001). Surgical treatment of diabetes mellitus by islet cell and pancreas transplantation. Postgrad. Med. J.
77: 383-387
[Full Text]
The European Study for the Prevention of Renal Dis,
(2001). Effect of 3 Years of Antihypertensive Therapy on Renal Structure in Type 1 Diabetic Patients With Albuminuria: The European Study for the Prevention of Renal Disease in Type 1 Diabetes (ESPRIT). Diabetes
50: 843-850
[Abstract][Full Text]
Fiorina, P., La Rocca, E., Venturini, M., Minicucci, F., Fermo, I., Paroni, R., D’Angelo, A., Sblendido, M., Di Carlo, V., Cristallo, M., Del Maschio, A., Pozza, G., Secchi, A.
(2001). Effects of Kidney-Pancreas Transplantation on Atherosclerotic Risk Factors and Endothelial Function in Patients With Uremia and Type 1 Diabetes. Diabetes
50: 496-501
[Abstract][Full Text]
Boffa, J.-J., Ying Lu, , Dussaule, J.-C., Chatziantoniou, C.
(2001). Improvements of renal lesions and function by angiotensin and endothelin receptor antagonism in nitric oxide-deficient rats. Journal of Renin-Angiotensin-Aldosterone System
2: S211-S216
[Abstract]
Luzi, L., Perseghin, G., Brendel, M. D., Terruzzi, I., Battezzati, A., Eckhard, M., Brandhorst, D., Brandhorst, H., Friemann, S., Socci, C., Carlo, V. D., Sereni, L. P., Benedini, S., Secchi, A., Pozza, G., Bretzel, R. G.
(2001). Metabolic Effects of Restoring Partial {beta}-Cell Function After Islet Allotransplantation in Type 1 Diabetic Patients. Diabetes
50: 277-282
[Abstract][Full Text]
Boffa, J.-J., Tharaux, P.-L., Dussaule, J.-C., Chatziantoniou, C.
(2001). Regression of Renal Vascular Fibrosis by Endothelin Receptor Antagonism. Hypertension
37: 490-496
[Abstract][Full Text]
White, S. A, Nicholson, M. L, Hering, B. J
(2000). Can islet cell transplantation treat diabetes?. BMJ
321: 651-652
[Full Text]
KOYA, D., HANEDA, M., NAKAGAWA, H., ISSHIKI, K., SATO, H., MAEDA, S., SUGIMOTO, T., YASUDA, H., KASHIWAGI, A., WAYS, D. K., KING, G. L., KIKKAWA, R.
(2000). Amelioration of accelerated diabetic mesangial expansion by treatment with a PKC {beta} inhibitor in diabetic db/db mice, a rodent model for type 2 diabetes. FASEB J.
14: 439-447
[Abstract][Full Text]
LENZ, O., ELLIOT, S. J., STETLER-STEVENSON, W. G.
(2000). Matrix Metalloproteinases in Renal Development and Disease. J. Am. Soc. Nephrol.
11: 574-581
[Full Text]
WILKINSON, A. H., COHEN, D. J.
(1999). Renal Failure in the Recipients of Nonrenal Solid Organ Transplants. J. Am. Soc. Nephrol.
10: 1136-1144
[Full Text]
Steffes, M.
(1999). Glomerular lesions of diabetes mellitus: preventable and reversible. Nephrol Dial Transplant
14: 19-21
ROSSINI, A. A., GREINER, D. L., MORDES, J. P.
(1999). Induction of Immunologic Tolerance for Transplantation. Physiol. Rev.
79: 99-141
[Abstract][Full Text]
Luzi, L.
(1998). Pancreas Transplantation and Diabetic Complications. NEJM
339: 115-117
[Full Text]
Ziyadeh, F. N., Hoffman, B. B., Han, D. C., Iglesias-de la Cruz, M. C., Hong, S. W., Isono, M., Chen, S., McGowan, T. A., Sharma, K.
(2000). Long-term prevention of renal insufficiency, excess matrix gene expression, and glomerular mesangial matrix expansion by treatment with monoclonal antitransforming growth factor-beta antibody in db/db diabetic mice. Proc. Natl. Acad. Sci. USA
97: 8015-8020
[Abstract][Full Text]
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