R. Goucha

Clinicopathological Characteristics of Obesity-associated Focal Segmental Glomerulosclerosis

Obesity-related glomerulopathy (ORG) is a secondary form of focal segmental glomerulosclerosis (FSGS) occurring in obese patients with a body-mass index higher than 30 kg/m2. It is typically manifested by nephrotic-range proteinuria without full nephrotic syndrome, and progressive renal insufficiency. Characteristic morphologic features include the consistent presence of glomerulomegaly, predominance of perihilar variant of FSGS, and the relatively mild fusion of visceral epithelial cell foot processes. The concept of podocyte depletion as a driver of the glomerular scarring in obesity-associated FSGS is well documented. The underlying mechanisms are likely to be related in part to the oxidative stress and the impairment of the integrity of the slit diaphragm and cell adhesion resulting mainly from angiotensin II and transforming growth factor-β. These proapoptotic cytokines are upregulated in obesity in response to insulin resistance, compensatory hyperinsulinemia and glomerular hyperfiltration-hypertension mediated mechanical stress. This review is designed to discuss the clinicopathologic features of obesity-associated FSGS, with a focus on the podocyte injury, which is involved in the onset and progression of the glomerulosclerotic process. Ultrastructural glomerular lesions are documented.

Risk factors and consequences of delayed graft function.

The impact of delayed graft function (DGF) on the outcome of renal transplantation remains controversial. We analyzed the risk factors for DGF and its impact on graft and patient survival. A total of 354 renal transplants performed between June 1986 and April 2000 were analyzed. Variables analyzed included donor and recipient age, method and duration of renal replacement therapy, HLA mismatch, cold and warm ischemia times, biopsy-confirmed acute rejection, length of stay in the hospital, serum creatinine at the end of first hospitalization as well as graft and patient survival at one, three, five and ten years. The study patients were divided into two groups: patients with DGF (G1) and those without DGF (G2). DGF occurred in 50 patients (14.1%), and it was seen more frequently in patients transplanted from deceased donors (60% vs. 40%, P <0.0001). The cause of DGF was acute tubular necrosis, seen in 98% of the cases. Univariate analysis showed a statistically significant difference between the two groups G1 and G2 in the following parameters: average duration on dialysis (52.3 vs. 36.4 months, P = 0.006), HLA mismatch (44.9% vs. 32.11% P = 0.015), donor age (35.9 vs. 40.2 years, P = 0.026), cold ischemia time (23 vs. 18.2 h, P = 0.0016), warm ischemia time (41.9 vs. 38.6 mn, P = 0.046), length of stay in the hospital during first hospitalization (54.7 vs. 33.2 days, P <0.0001), serum creatinine at the end of first hospitalization (140 vs. 112 μmol/L, P <0.0001) and at three months following transplantation (159 vs. 119 μmol/L, P = 0.0002). Multivariate analysis revealed the following independent risk factors for DGF: deceased donor (RR = 13.2, P <0.0001) and cold ischemia time (RR = 1.17, P = 0.008). The graft survival at one, three, five and ten years was 100%, 93%, 88.3% and 78.3% in G1 versus 100%, 95.9% 92.8% and 82.3% in G2; there was no statistically significant difference. The patient survival at one, three, five and ten years was 100%, 91.3%, 83.6% and 74.4% in G1 versus 100%, 95.9%, 94% and 82.6% in G2 with a statistically significant difference (P = 0.04). Prolonged cold ischemia time and transplantation of kidneys from deceased donors were the main risk factors for DGF in our study. Also, DGF significantly affected patient survival but had no influence on graft survival.

Acute renal failure by ingestion of Euphorbia paralias

Euphorbia paralias is known in traditional medicine as an anti-inflammatory agent, a purgative and for its local anesthetic property. To the best our knowledge, renal toxicity of this substance has not been previously reported. In this paper, we report the case of a 29-year-old male who developed renal damage following ingestion of Euphorbia paralias. He had been on follow-up for nephrotic syndrome since 1986, although irregularly, with several relapses but each responding well to steroid therapy. A kidney biopsy had not been performed earlier due to refusal by the patient. He was off steroids since April 2008 because the patient developed osteoporosis. He was admitted with general malaise and oliguria to our department in May 2009, following repeated vomiting and watery diarrhea for three days. On examination, he was edematous but had normal vital signs except for a pulse rate of 120/min. Hemoglobin was only 5.5 g/dL but with normal white cell and platelet counts. Blood biochemistry showed evidence of advanced renal failure with a serum creatinine level of 1835 μmol/L and urea at 44.6 mmol/L, sodium of 132 μmol/L and potassium at 4.3 mmol/L. He had features of nephrotic syndrome with severe hypoproteinamia and 24-h urinary protein of 10.45 g. Ultrasonography revealed enlarged kidneys with a reduced echogenecity of the medulla and the papillae. Subsequently, after hemodialysis with blood transfusion, a kidney biopsy was performed that showed focal segmental glomerulosclerosis associated with an acute tubular injury. On intensive interrogation, the patient gave a history of ingesting boiled Euphorbia paralias as a native treatment for edema, ten days prior to the onset of the current illness. A diagnosis of acute renal failure (ARF) resulting from the possible nephrotoxic effect of Euphorbia paralias poisoning was made. He was treated with intermittent hemodialysis and corticosteroids. Serum creatinine values improved after 48 days. At six months following the intoxication, serum creatinine of the patient was 240 μmol/L. In cases of unexplained ARF, a toxic mechanism should always be considered and acute renal failure caused by Euphorbia paralias should be included as a cause if renal toxicity is suspected in those places where it is being used as a native medicine.

Kidney Transplantation: Charles Nicolle Hospital Experience

The aim of our retrospective study was to analyze the short- and long-term follow-up of 298 renal transplantations performed between June 1986 and May 2005. All were first transplantations except 4 cases, with 54 from cadaveric and 244 from living donors. The recipients included 196 males and 102 females of overall mean age of 31.21 +/- 8.9 years (range, 16-61 years). A combination of prednisolone and azathioprine was presented for 212 patients or mycophenolate mofetil for 86 patients. Polyclonal or monoclonal antibodies were used as induction therapy in 183 cases. Cyclosporine was administered to 188 cases and tacrolimus only to 16. HLA matching was 0 mismatches (MM) in 65 cases; 1 or 2 MM in 113; 3 MM in 99; and > or =4 MM in 21. Acute tubular necrosis occurred in 45 cases. One hundred eighteen patients experienced at least 1 acute rejection episode: 102 cases (41.8%) among living and 16 (29.6%) among cadaveric kidneys donor (P = .0007). The actuarial patient and graft survival rates at 1, 5, 10, 15, and 20 years were 95.9%, 87.4%, 77.5%, 65.6%, and 60.8%, and 94.9%, 84.5%, 75.4%, 65.4%, and 53%, respectively. Sixty-three patients died and 72 patients returned to dialysis. Our results were comparable to experienced centers. However, the member of kidney transplantations does not match the increased number of patients on renal replacement therapy. It is advisable to promote obtaining organs from brain-dead donors.

Value of Electron Microscopy in the Diagnosis of Glomerular Diseases

To evaluate the contribution of electron microscopy to the final diagnosis of glomerulopathies, the authors established a prospective study during the first semester of 2006. A total of 52 kidney biopsies were performed with 3 samples for light microscopy, immunofluorescence, and electron microscopy. Among these renal biopsies, only 20 were examined with electron microscopy because the diagnosis made on the basis of conventional methods had remained unclear or doubtful. In 18 cases, electron microscopy was undertaken for the investigation of primary kidney disease. The 2 remaining cases were transplant biopsies. In this series of 20 patients, there were 3 children with an average age of 9 years and 17 adults with an average age of 35.5 years. Fifteen patients (75%) were nephrotic. The study revealed that electron microscopy was essential for diagnosis in 8 cases (40%) and was helpful in 12 cases (60%). In conclusion, the results showed that the ultrastructural study provides essential or helpful information in many cases of glomerular diseases, and therefore electron microscopy should be considered an important tool of diagnostic renal pathology. As was recommended, it is important to reserve renal tissue for ultrastructural study unless electron microscopy can be routinely used in all biopsies. Thus, this technique could be performed wherever a renal biopsy has to be ultrastructurally evaluated.

Nephrolithiasis-induced end stage renal disease.

Introduction: Nephrolithiasis still remains a too frequent and underappreciated cause of end stage renal disease (ESRD). Methods and patients: Of the entire cohort of 7128 consecutive patients who started maintenance dialysis in our nephrology department between January 1992 and December 2006, a total of 45 patients (26 women, 19 men) had renal stone disease as the cause of ESRD. The type of nephrolithiasis was determined in 45 cases and etiology in 42. The treatment and evolution of stone disease and patient’s survival were studied. Results: The overall proportion of nephrolithiasis related ESRD was 0.63%. The mean age was 48.4 years. Infection stones (struvite) accounted for 40%, calcium stones, 26.67% (primary hyperparathyroidism:15.56%; familial hypercalciuria: 4.44%, unknown etiology: 6.66%), primary hyperoxaluria type 1, 17.78% and uric acid lithiasis in 15.56% of cases. The mean delay of the evolution of the stone renal disease to chronic renal failure was 85.8 months. The feminine gender, obesity and elevated alkaline phosphatases >128 IU/L were significantly correlated with fast evolution of ESRD. The median evolution to ESRD was 12 months. The normal body mass index (BMI), medical treatment of stone and primary hyperoxaluria type 1 were correlated with fast evolution to ESRD. All patients were treated by hemodialysis during a mean evolution of 60 months. Sixteen patients died. The patients survival rate at 1, 3 and 5 years was 97.6, 92.8 and 69% respectively. Hypocalcemia, cardiopathy and normal calcium-phosphate product were significantly correlated with lower survival rate. Conclusion: Severe forms of nephrolithiasis remain an underestimated cause of ESRD. These findings highlight the crucial importance of accurate stone analysis and metabolic evaluation to provide early diagnosis and efficient treatment for conditions leading to ESRD.

Membranoproliferative Glomerulonephritis with Isolated C3 Deposits: Case Report and Literature Review

Membranoproliferative glomerulonephritis with isolated C3 deposits (MPGNC3) is an uncommon condition characterized by overt glomerular C3 deposits in the absence of immunoglobulins and intramembranous dense deposits. Here the authors describe the clinical and morphological features of primary MPGNC3 in a 13-year-old boy and critically review the previously published cases. The patient presented with nephrotic syndrome and microscopic hematuria. Blood tests revealed very low circulating C3 levels. The renal biopsy exhibited subendothelial, subepithelial, and mesangial deposits, with C3 but not immunoglobulins seen on immunofluorescence. This case and the review of the literature indicate that the serum complement profile with decreased levels of C3 and normal levels of classical pathway components together with glomerular deposits containing exclusively complement C3 is highly suggestive of alternative pathway activation. The diagnosis of acquired and/or genetic complement abnormalities in some cases supports that complement dysregulation is implicated in the pathogenesis of MPGNC3. Such data show great promise to provide new therapy strategies based on modulation of the complement system activity.

Short- and long-term post–renal transplant follow-up at Charles Nicolle Hospital

years, 56.5%; 31 to #45 years, 33.5%; and .45 years, 4%. Primary renal disease was chronic glomerulonephritis in 85 cases (42.5%), chronic pyelonephritis in 43 (21.5%), nephroangiosclerosis in 17 (8.5%), hereditary nephropathy in 11 (5.5%), and unknown in 44 (22%). Initial renal replacement therapy (RRT) was hemodialysis (HD) in 155 cases (77.5%), continuous ambulatory peritoneal dialysis (CAPD) in 24 (12%) and the two techniques combined in 21 (10.5%). For LRD, only first-degree relatives who gave their informed consent were accepted. All patients received ABO compatible and cross-match negative kidneys. At least 3 units of blood transfusions were given to 161 patients (80.5%) and cytotoxic antibodies were screened. All patients received a combination of prednisolone: 2 mg/kg/d on day 0, tapered to 0.2 mg/kg/d on day 90 and azathioprine at 125 mg/d. Antilymphocyte globulin (ALG) or antithymocyte globulin (ATG) was used as prophylactic treatment of graft rejection in 98 cases (48%) during the first 15 days. Cyclosporine was administered in 112 patients (56%) twice daily orally at 5 mg/d beginning on day 3 to 15 days in LRD transplants with one identical haplotype and after corticoresistant acute rejection episodes. The dosages were adjusted to clinical state and cyclosporine blood level (radioimmunoassay). Acute rejection episodes were treated with a combination of pulses of methylprednisolone and ALG/ATG in 75 cases. OKT3 was introduced in six cases when ALG/ATG failed to reverse the rejection. Mycophenolate mofetil was used in 11 cases with cyclosporine nephrotoxicity. The results were expressed as mean 6 standard deviation (SD). Comparisons were made with chi squared test for categorical variables and PLSD Fisher’ test for continuous variables. The survival rates were computed using the actuarial method. P , .05 was considered statistically significant. RESULTS The waiting time on dialysis was 28 6 22 months (1 to 119 months). For LRD, the donors were 96 (52.7%) siblings, 84 (46.2%) parents, and 2 children. HLA matching was 0 mismatches (MM) in 48 cases (26.4%) and 3 MM in 134 (73.6%). Their mean age was 38.6 6 13.4 (16 to 65) years. For CAD, HLA matching was 1 to 6 MM. The cytotoxic antibodies were positive in 27% of cases. Acute tubular necrosis (ATN) occurred in 26 cases (14.3%) of LRD and in 3 (16.7%) CAD. All those patients were hemodialyzed requiring 1 to 10 sessions, but all recovered. The difference between the two groups was not statistically significant (P 5 .07). The mean time of warm ischemia was 44 6 13 minutes for patients who have expressed ATN and 41.9 6 10.9 for those without ATN. The mean time of cold ischemia for CAD was 26.8 6 6 hours. Acute rejection was encountered in 16 (33.3%) cases of LRD with 0 MM, 80 (59.7%) cases of LRD with 3 MM, and 14 (77.8%) cases in the CAD group. The differences between the three groups were statistically significant (P , .0009). Complications Infectious complications were very common (86% of cases). Viral infections occurred in 40% of cases, mostly CMV (21%) and herpes (14%). No HIV infection was seen. Bacterial infections occurred in 60% of cases, mostly urinary tract infections (49%), septicemia (11.5%), and bronchopulmonary infections (5%). Six patients had scabies. Urologic complications occurred in 31 cases: 14 (7%) urinary leaks, 6 (3%) urinary stenosis, 2 ureteral compressions, 4 lymphoceles, 3 urinary lithiasis, and 2 urinary tuberculosis. Vascular complications were seen in eight cases: two arterial thrombosis, two venous thrombosis, three arteriovenous fistulae, and one perirenal hematoma. We noted recurrence of focal segmental glomerulosclerosis in six cases and glomerulonephritis de novo in two cases.

Four successful pregnancies following kidney transplantation.

Between June 1974 and October 1998, 325 renal TR were performed. There were 225 males and 100 females. Eighty-two females had an age between 20 and 40 years, 45 of them were married, and only 15 willing to be pregnant. During the period of study, 12 PG were observed in eight women. Eight PG were terminated during the first quarter for various reasons. Only three women had a total of four successful PG. Their ages were 25, 27, and 31 at TR. Their primary renal disease was IgA nephropathy, glomerulonephritis, and indeterminate in the third woman. The interval between TR and PG was 12 years for the first patient (P1), 2 and 4 years for the second patient (P2), and 4 years for the third patient (P3). P1 and P3 received kidneys from cadaveric donors and P2 from a liverelated donor. P1 and P2 were treated with 10 mg/day of corticosteroids (CT), 125 mg/day of azathioprine (AZA), and antithymocyte globulin (ATG). P3 received 10 mg/day of CT, ATG, and 300 mg/day of cyclosporine A (CyA).

Nodular glomerulosclerosis in patients' without history of diabetes mellitus: a case report.

IntroductionDiabetic nephropathy can occur during the course of both type1 and type 2 diabetes mellitus. The characteristic lesions are diffuse or nodular (Kimmelsteil-Wilson) diabetic glomerulosclerosis. The reported cases represent unusual presentations of diabetes mellitus.Case presentationWe report the case of a 49-year-old man without prior history of diabetes mellitus who presented with rapidly progressive renal failure and whose renal biopsy revealed nodular (Kimmelsteil-Wilson) glomerulosclerosis lesions characteristic of diabetes.ConclusionRenal manifestations of diabetes mellitus may antedate other more common presenting symptoms of this disease and we critically review the literature on this subject.