Spectrum of Non diabetic kidney disease in patients with type 2 diabetes and its clinicopathological correlation.
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Diabetes mellitus (DM) is the leading cause of chronic kidney disease worldwide chiefly attributable to diabetic nephropathy (DN). In these patients, non diabetic kidney disease (NDKD) can also occur either alone or superimposed on diabetic nephropathy. This study aimed to identify the prevalence and the etiology of NDKD in our center and also the clinical and laboratory parameters to help distinguish these two entities.This was a cross sectional observational study. A total of 47 patients were enrolled in the study during the study period. In all the patients, kidney biopsy was done because of atypical presentations and was examined by light and immunofluorescence microscopy. The clinical & laboratory parameters and the biopsy findings were recorded in a standard proforma.A total of 47 patients (male/female: 34/13 and mean age 52.11±9.36) were included in the study. The chief co morbidity was hypertension which was present in 61.7% of patients. The most common indication of biopsy was nephrotic presentation (38.3%) followed by nephritic illness (25.5%). The prevalence of NDKD in our study cohort was 85.1% of which isolated NDKD was 57.4% and NDKD + DN was 27.7%. The most common histological lesion were membranous glomerulopathy and focal segmental glomerulosclerosis (FSGS) each with a frequency of 15% followed by chronic tubulointerstitial nephritis (CTIN), IgA nephropathy and others. There was significant difference in the median duration of diabetes in these groups and it was around 5 years less in the NDKD group. There was no difference among three groups in term of eGFR, HbA1C and proteinuria.Our study demonstrated a high prevalence of NDKD in the patients with type 2 diabetes. The duration of diabetes was the strongest predictor of NDKD. Kidney biopsy should be undertaken liberally whenever there is strong clinical suspicion especially in the presence of atypical features. The exact histological diagnosis can clarify the further treatment planning as well as the prognosis.Keywords:
Glomerulopathy
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A 64-yr-old man presented with diabetes mellitus, proteinuria, hypertension and moderate renal dysfunction. Renal biopsy revealed diabetic glomerulosclerosis (diffuse lesion), IgA nephropathy and membranous nephropathy (stage 2). Both mesangial IgA and subepithelial IgG deposits were demonstrated by immunofluorescence and immunoelectron microscopy. Electron microscopic studies by immunogold method showed localization of IgA (diameter 15nm gold particles) within mesangial dense deposits and IgG (diameter 15nm gold particles) within subepithelial dense deposits. Overlapping IgA and membranous nephropathy was revealed in the same diabetic glomeruli with functional and biochemical alternations.
Immunogold labelling
Immunoelectron microscopy
Membranous Nephropathy
Glomerulosclerosis
Immunofluorescence
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Immune complex
Immunofluorescence
Membranoproliferative glomerulonephritis
Nephritis
Interstitial nephritis
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The association of diabetic nephropathy with primary glomerulonephritis is rare. Several reports have shown that primary glomerulonephritis can be superimposed on diabetic nephropathy. These glomerulonephritis include idiopathic membranous glomerulonephritis, IgA glomerulonephritis, Henoch-Schonlein nephritis, membranoproliferative glomerulonephritis, lupus nephritis, minimal change disease, postinfectious glomerulonephritis and rapidly progressive glomerulonephritis. Because some of these disorders can alter the management and prognosis of renal disease in diabetic patients, the appearance of urinary abnormalities (hematuria, atypical nephrotic syndrome) or deterioration in renal function inconsistent with the natural history of diabetic nephropathy raises the possibility of a nondiabetic renal disease and should lead to a more detailed evaluation. We report a patient with type I diabetes that underwent a renal biopsy because of the heavy proteinuria and nephrotic syndrome. Renal biopsy showed diabetic nephropathy coexistent with focal segmental glomerulosclerosis. To the best of our knowledge, this is the first reported case of primary focal segmental glomerulosclerosis associated with diabetic nephropathy and diabetic retinopathy, with excellent therapeutic response.
Membranoproliferative glomerulonephritis
Minimal change disease
Membranous Nephropathy
Rapidly progressive glomerulonephritis
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The prevalence of diabetic patients with endstage renal disease is increased overall the word. Renal biopsy is sometimes necessary to precise the type of renal damage.To precise the type and the frequency of non diabetic nephropathy in diabetic patients.We enrolled retrospectively during 17 years, 72 diabetic patients who had a renal biopsy.A non diabetic nephropathy was found in 69.5 % of them. Its presence was correlate to the presence of hematuria and the absence of diabetic retinopathy. We can successfully treated nine patients with minimal-change nephrotic syndrome and one patient with crescentic glomerulonephritis.Renal biopsy must be done in diabetic patient with hematuria or in the absence of diabetic retinopathy.
Renal pathology
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Collapsing glomerulopathy is an aggressive form of glomerular disease defined for its histopathological features of glomerular collapse, visceral epithelial cell damage and tubulointerstitial changes that are characteristic. Patients with collapsing glomerulopathy present with severe nephrotic syndrome, marked proteinuria, generally more than 10 g/day and rapid progression to chronic renal failure, or death due to complications of nephrotic syndrome, despite any form of treatment. Collapsing glomerulopathy presents as de novo or recurrent disease in the renal allograft. There is slight predominance in males and strong predominance in blacks as renal diseases in general. Collapsing glomerulopathy shares several clinical and histopathological features with focal and segmental glomerulosclerosis and HIV-nephropathy; nevertheless, there is enough evidence to support collapsing glomerulopathy as a different entity. It must be mentioned that collapsing glomerulopathy, focal and segmental glomerulosclerosis and HIV-nephropathy may have a similar pathophysiological mechanism of damage to the visceral epithelial cell.
Glomerulopathy
Glomerulosclerosis
Minimal change disease
Membranous Nephropathy
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The aim of this retrospective study was to evaluate the results of the immunosuppressive regiment in managing of IgA nephropathy associated with primary nephrotic syndrome at the Nephrology Clinic, University of Sarajevo Clinics Centre in period of 1997-2007. We studied 19 patients (4 women and 15 men) with idiopathic nephrotic syndrome, where pathomorphologic changes of IgA nephropathy were proved by kidney biopsy. The levels of diuresis, proteinuria, albuminemia, lipidemia and kidney function, as measure of efficiency of used therapy, were monitored. The IgA nephropathy present with the nephrotic syndrome was shown in 15.8% (19) patients underwent renal biopsy due to primary nephrotic syndrome in the period of observation. The average age of patients with IgA nephropathy was 34.9+/-14.1 years. Eight patients from this group were treated with corticosteroid therapy (1-1.5 mg/kg of body weight for 4 weeks, followed by 0.5 mg/ kg of body weight until therapeutic response was achieved, and finally gradual exclusion of therapy after eight weeks in responsive patients), 6 patients with corticosteroids and bolus cyclophosphamide (10-15 mg/kg BW), and in 5/19 patients cyclosporine therapy was used (3 mg/kg BW). Complete remission of nephrotic syndrome was achieved in 42.1% of the patients. In conclusion, in adults patients with primary nephrotic syndrome associated with IgA nephropathy, used immunosuppressive therapy resulted in a high percentage of achieved remissions.
Immunoglobulin A
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To identify clinical and immunological risk factors underlying the development of renal involvement in primary Sjögren's syndrome (pSS).Seventy-eight patients (75 females, 3 males) with pSS were carefully interviewed and clinical and laboratory data from the time of diagnosis recorded. The baseline data on patients shown to have either latent or overt distal renal tubular acidosis (dRTA), mild proteinuria or increased urinary excretion of alpha-1 microglobulin (alpha1m) after a mean disease duration of 9 +/- 4 years, were compared to the baseline data on those who did not have these manifestations at follow-up.Patients with subsequent latent or overt dRTA were found to have significantly higher baseline levels of serum total gamma-globulin (24 +/- 7 vs. 19 +/- 6 g/l, p = 0.011) and serum protein (84 +/- 7 vs. 79 +/- 7 g/l, p = 0.024) compared to those with normal renal acidification capacity. The baseline levels of serum beta-2 microglobulin (beta2m) were higher in patients with an acidification defect than in those with normal acidification capacity (3.1 +/- 1.1 vs. 2.6 +/- 0.8 mg/l, p = 0.072). In those with subsequent proteinuria the levels of serum beta2m were almost significantly higher at baseline as compared to those with normal urinary protein excretion (3.1 +/- 1.4 vs. 2.5 +/- 0.8 mg/l, p = 0.052). The subgroup of pSS patients who had increased urinary alpha1m excretion as a sign of tubular proteinuria, had higher baseline levels of ESR (55 +/- 27 mm/h vs. 40 +/- 23 mm/h, p = 0.076) and significantly higher baseline levels of serum beta2m (4.6 +/- 1 .8 vs. 2.6 +/- 0.8 mg/l, p = 0.029) as compared to those with normal urinary alpha1m excretion.High levels of serum total gamma-globulin, serum protein and serum beta2m were the best predictors of the development of dRTA in pSS patients. High baseline levels of serum beta2m were also associated with the subsequent occurrence of mild proteinuria and increased urinary alpha1m excretion in patients with pSS.
Beta-2 microglobulin
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Pregnancy in chronic kidney disease (CKD) patients is often associated with hypertension and/or the worsening of renal function and neonatal death. The present study explored the clinical characteristics of predictive factors for hypertension in biopsy-proven IgA nephropathy patients with superimposed preeclampsia (SPE).The subjects were 34 Japanese women with IgA nephropathy whose renal specimen for histological tests was obtained before pregnancy. We retrospectively investigated the relevant clinical factors to explain a rise in blood pressure (BP). The histological findings were evaluated with respect to the quantitative measurements of both global glomerulosclerosis and interstitial damage.Renal biopsies before pregnancies showed that the global glomerular sclerosing index and interstitial damage in the SPE group were significantly higher than in the normal group. The prevalence of SPE was 38.2 % (normal pregnancy 21, SPE 13 cases). The neonatal death rate was 3.0 % (1/34)overall. Just before conception, systolic blood pressure (SBP), serum creatinine (Cr)and blood urea nitrogen (BUN) concentration in the SPE were significantly higher than in normal pregnancies. In contrast, CCr and eGFR were lower in the SPE group than in the normal group. At delivery, serum Cr, BUN and uric acid (UA) concentration in the SPE group were significantly higher than in the normal group. In contrast, CCr and eGFR were lower in the SPE than in the normal group. At delivery, correlation analysis revealed a significant correlation between SBP or diastolic BP (DBP) and the histological severity, between SBP or DBP and daily protein excretion, and between SBP or DBP and serum Cr concentration. With respect to the birth weight of newborns, there was a significant negative correlation between the birth weight and the global glomerular sclerosing rate, and between the birth weight and serum Cr concentration or BUN. A stepwise multiple regression analysis showed that predictive factors for a rise in SBP during pregnancy were the degree of interstitial damage and daily urinary protein excretion. These results suggest that renal function, the magnitude of urinary protein excretion, serum Cr, BUN, UA concentrations, and the severity of histological abnormalities are all associated with SPE occurrence. The predictors of a rise in BP were interstitial damage and urinary protein excretion at pregnancy. In addition, Receiver Operating Characteristic (ROC) analysis showed that both glomerular sclerosis and interstitial damage could be potential predictors for SPE.Histological severity in renal biopsy, urinary protein excretion and renal function are associated with SPE in patients with IgA nephropathy. Among these associations, the histological findings and urinary protein excretion may serve as useful predictors for a rise in BP.
Blood urea nitrogen
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