Genetic analysis of Iranian autosomal dominant polycystic kidney disease: new insight to haplotype analysis.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) caused by mutations in two PKD1 and PKD2 genes. Due to the complexity of the PKD1 gene, its direct mutation screening is an expensive and time-consuming procedure. Pedigree-based haplotype analysis is a useful indirect approach to identify the responsible gene in families with multiple affected individuals, before direct mutation analysis. Here, we applied this approach to investigate 15 appropriate unrelated ADPKD families, selected from 25 families, who referred for genetic counseling. Four polymorphic microsatellite markers were selected around each PKD1 and PKD2 loci. In addition, by investigating the genomic regions, two novel flanking tetranucleotide STR markers were identified. Haplotype analysis and calculating Lod score confirmed linkage to PKD1 in 9 families (60%) and to PKD2 in 2 families (13%). Linkage to both loci was excluded in one family (6.6%). In 2 families (13%) the Lod scores were inconclusive. Causative mutation was identified successfully by direct analysis in two families with confirmed linkage, one to PKD1 and another to PKD2 locus. The study showed that determining the causative locus prior to direct mutation analysis is an efficient strategy to reduce the resources required for genetic analysis of ADPKD families. This is more prominent in PKD2-linked families. Selection of suitable markers, and appropriate PCR multiplexing strategy, using fluorescent labeled primers and 3 primer system, will also add value to this approach.

Chronic kidney disease after hematopoietic cell transplantation: frequency, risk factors, and outcomes.

BACKGROUND: Occurrence of chronic kidney disease (CKD) after hematopoietic cell transplantation (HCT) is rare with relatively few reported cases. The aim of this study was to evaluate the frequency of CKD among patients who received HCT for hematologic and nonhematologic disorders. OBJECTIVE: We performed a prospective study to evaluate the frequency of CKD and its risk factors. Between 1997 and 2006 there were 1693 patients engrafted at the Bone Marrow Transplant Research Center. METHOD: CKD was defined as a doubling of serum creatinine level from the baseline and after 1 year from receiving a transplantation. The risk of CKD in relation to a non-based total body irradiation conditioning regimen, the type of graft (allograft autograft), and the incidences of graft-versus-host disease (GVHD), drug toxicity, and veno occlusive disease (VOD) were examined in 1963 HCT patients. RESULTS: Kidney involvement developed in 66 patients (4%). By 6-12 months after HCT, approximately 33% of these patients developed CKD (23 patients: 19 allograft and 4 autograft). In most CKD patients, the cause was idiopathic. In 23 patients who developed CKD, 5 patients had acute kidney injury during the transplantation period with GVHD. Other renal involvements were as follows: hypertension (17%), proteinuria (15%), hydronephrosis (2%), hematuria (18%), and diabetes (3%). CONCLUSION: The frequency of CKD in this study seems to be high. It is important to know the specific type of kidney damage, to determine when to be aware of the time of occurrence of renal complications and to understand the best methods to treat patients with renal injury secondary to nephrotic syndrome and idiopathic CKD.

Association of hyperglycemia on allograft function in the early period after renal transplantation.

Hyperglycemia is common following renal transplantation. This study was conducted to evaluate the relationship of perioperative serum glucose levels and acute rejection in 100 nondiabetic patients who underwent renal transplantation. Blood glucose was measured immediately following surgery and every 6 hours during the first 48 hours posttransplant as well as for 1 month to evaluate occurrence of acute rejection episodes (ARE). The rate of ARE was 33%. The mean blood glucose level immediately after surgery in patients with versus without ARE was 249.67 +/- 61.78 and 184.82 +/- 73.35 mg/dL, respectively (P=.000). There was no significant correlation between ARE and donor or recipient age or sex, delayed graft function, type of donor, or treatment. This study suggested a correlation between immediate blood glucose and ARE. In this regard, blood glucose monitoring and control during operation and immediate postoperatively may reduce the acute rejection rate.