PKD2 mutation in an Iranian autosomal dominant polycystic kidney disease family with misleading linkage analysis data

BACKGROUND: Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic renal disorder caused by mutation in 2 genes PKD1 and PKD2. Thus far, no mutation is identified in approximately 10% of ADPKD families, which can suggest further locus heterogeneity. Owing to the complexity of direct mutation detection, linkage analysis can initially identify the responsible gene in appropriate affected families. Here, we evaluated an Iranian ADPKD family apparently unlinked to both PKD1 and PKD2 genes. This is one of the pioneer studies in genetic analysis of ADPKD in Iranian population. METHODS: Linkage reanalysis was performed by regenotyping of flanking microsatellite markers in 8 individuals of the ADPKD family. Direct mutation analysis was performed by Sanger sequencing. RESULTS: Mutation analysis revealed a pathogenic mutation (c.1094+1G>A) in the PKD2 gene in the proband. Analyzing 2 healthy and 4 clinically affected members confirmed the correct segregation of the mutation within the family and also ruled out the disease in 1 suspected individual. Misinterpretation of the linkage data was due to the occurrence of 1 crossing over between the PKD2 intragenic and the nearest downstream marker (D4S2929). Homozygosity of upstream markers caused the recombination indistinguishable. CONCLUSION: Although analysis of additive informative polymorphic markers can overcome the misleading haplotype data, it is limited because of the lack of other highly polymorphic microsatellite markers closer to the gene. Direct mutation screening can identify the causative mutation in the apparently unlinked pedigree; moreover, it is the only approach to achieve the confirmed diagnosis in individuals with equivocal imaging results.

Renal involvement in patients with hepatitis c virus infection

Hepatitis C virus [HCV] infection is a hepatotropic virus causing a variety of extrahepatic immunological manifestations and is a risk factor of a variety of extrahepatic diseases, such as mixed cryoglobulinemia and membranoproliferative glomerulonephritis [MPGN], which is the most common glomerulonephritis. The aim of this study was to evaluate renal involvement in HCV-infected patients. A total of 300 randomly-selected HCV antibody-positive outpatients at the HCV clinic of Shariati hospital were enrolled. Serum creatinine was measured and glomerular filtration rate was estimated accordingly. Urine proteinuria was measured in 24-hour urine samples. The patients were 249 men [83.2%] and 51 women [16.8%] with a mean age of 37.8 +/- 11.7 years [range, 18 to 70 years]. Proteinuria was found in 12 HCV antibody-positive adults [4%], 1 of whom underwent biopsy. He was a 55-year-old man with a 4-month history of facial and lower extremities edema and 3-g proteinuria with a normal kidney function [glomerular filtration rate, 85 mL/min] and normocomplementemia. Kidney biopsy specimens showed MPGN. The frequency of low glomerular filtration rate was 0.7% [2 patients] in the HCV antibody-positive adults. There was no significant relationship between HCV seropositivity and low glomerular filtration rate. Our observations showed renal involvement in HCV antibody-positive patients. Among immune complex glomerular kidney diseases, MPGN without cryoglobulins is thought to be the most common in these patients

Frequency, risk factors, and outcome of acute kidney injury following bone marrow transplantation at dr shariati hospital in Tehran

Bone marrow transplantation [BMT] is a major modality for malignant and hematologic disorders. This procedure is associated with a high morbidity and mortality such as acute kidney injury [AKI]. Many factors, such as therapeutic agents, irradiation, and graft versus host disease [GVHD] can cause AKI. Bone marrow transplantation conditioning therapy in Iran is based on drugs such as busulfan and cyclophosphamide and without irradiation therapy. The aim of this study was to evaluate the frequency, risk factors, and mortality of AKI among patients who underwent BMT. Acute kidney injury was defined as doubling serum creatinine from baseline at any time during the first 180 days posttransplant. The risk of AKI in relation to non-total-body-irradiation-based conditioning regimen, type of graft [allograft and autograft], comorbidities, GVHD, drug toxicity, and veno-occlusive disease were examined in 375 patients with BMT. One hundred and forty-two patients [37.6%] developed AKI at a median of 18 days after transplant. A higher frequency of AKI was observed in patients who received cyclosporine A [40%], patients with allograft BMT [42.1%], and those who developed gastrointestinal GVHD [47.3%] .The remainder AKI cases were associated with amphotericin B, veno-occlusive disease, and hemolytic-uremic syndrome. The frequency of AKI in our patients with BMT remained high. Cyclosporine A and amphotericin B and the presence of GVHD and veno-occlusive disease increased the risk of AKI within the first 180 days after BMT

Predictors of patient survival in continuous ambulatory peritoneal dialysis 10-year experience in 2 major centers in Tehran

Many factors have been proposed to be associated with higher mortality in patients on continuous ambulatory peritoneal dialysis [CAPD]. However, the relative importance of these factors may differ among patients with different characteristics. We evaluated survival of patients on CAPD and its influencing factors in Iran. We enrolled 282 patients on CAPD between 1996 and 2006 at 2 major CAPD centers in Tehran. Patient survival was investigated during this period. Demographic characteristics, laboratory data, dialysis adequacy parameters, residual renal function, peritoneal transport characteristics, and nutritional status were assessed as potential predictors of the outcome. The mean duration of follow-up was 18.4 +/- 14.5 months. Sixty patients [21%] died during the studied period. In univariate analysis, age, body mass index, history and duration of hemodialysis before CAPD, diabetes mellitus, blood pressure, patient selection criteria, edema, peritonitis, renal residual function, urine volume, dialysis adequacy, and serum levels of cholesterol, triglyceride, intact parathyroid hormone, calcium, and albumin were predictors of patient survival. Multivariate analysis demonstrated that old age, diabetes mellitus, prior hemodialysis longer than 7 months, low serum albumin, calcium, trigelyceride, and parathyroid hormone levels independently predicted mortality, while the use of angiotensin-converting enzyme inhibitors was associated with a better survival. This study showed that older patients on CAPD and diabetics are at a higher risk of mortality. On the other hand, nutritional and metabolic factors are other predictors of mortality. Especial concern should be applied to good nutrition and treatment of comorbidities in these patients