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.

[ predictive value of neutrophil gelatinase-associated lipocalin [NGAL] in early diagnosis of contrast-induced nephropathy upon angioplasty/ angiography]

Neutrophil Gelatinase Associated Lipocalin [NGAL] is a new biomarker which can predict acute kidney injury [AKI] in critically ill patients. Usefulness of NGAL in the early diagnosis of all types of AKI is under question. We hypothesized NGAL is an early predictive biomarker of contrast-induced nephropathy [CIN]. In this process evaluation study, we enrolled 122 patients [Mean age 59.7 +/- 10.8 years] undergoing elective angiography/angioplasty with contrast media during April to September 2009. Serial urine samples were analyzed in a double-blind fashion by NGAL enzyme-linked immunosorbent assay. CIN was defined as a 25% increase in baseline serum creatinine. The prevalence of CIN was 30.3%. Significant elevations in urinary NGAL concentrations were noted within 12-h and 24-h after the procedure in patients with CIN. NGAL concentrations after 12 hours was 90.62 +/- 105.63 vs. 27.6 +/- 45.8 ng/ml in patients with and without CIN, respectively P=0.0001, and 79.78 +/- 117.7 vs. 30.92 +/- 52.84 ng/ml, 24 hours afterwards P=0.002. Some patients had AKI after five days of exposure rather than the second day [P=0.0001]. We found using a cut-off point of 8 ng/ml with a sensitivity, specificity, negative predictive value and area under the ROC curve 94%, 25%, 91% and 0.75 respectively are good for the prediction of CIN in 12-h urinary NGAL and a cut-off point of 5.5 ng/ml with respective values of 97%, 24%, 95% and 0.70 for 24-h urinary NGAL. Urine NGAL may represent a sensitive early biomarker of acute AKI after angiography/angioplasty. We recommend the routine measurement of NGAL in high risk patients receiving contrast agents

Serum levels of lipoprotein [A] and homocysteine in patients on hemodialysis who take hydroxymethylglutaryl-CoA reductase inhibitors, vitamin B6, and folic acid

High serum levels of lipoprotein [a] and homocysteine are risk factors of cardiovascular disease which are prevalent in patients on hemodialysis. Controversy exists about the effects of hydroxymethylglutaryl-CoA reductase inhibitors on serum lipoprotein [a] levels in patients on hemodialysis. Also, deficiency of some water soluble vitamins and administration of statins may raise serum levels of homocysteine in these patients. This study was designed to investigate serum levels of lipoprotein [a] and homocysteine in patients on hemodialysis who were taking a statin, vitamin B6, and folic acid. We investigated on 152 patients with maintenance hemodialysis who were taking atorvastatin or lovastatin, vitamin B6, and folic acid for at least 6 months. Their serum levels were obtained to measure lipoprotein [a] and homocysteine levels, as well as triglyceride, total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The mean serum values of total cholesterol, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol and triglyceride were significantly less than the maximum reference values [P < .001]. The mean serum level of lipoprotein [a] was also less than the reference value [P = .009], but homocysteine level was 33% higher on average than the reference value [P < 001]. Our study demonstrated that in our patients on hemodialysis, the mean serum level of homocysteine was about 30% higher than the reference value although they were receiving vitamin B6 and folic acid. Hence, they were still exposed to the risk of cardiovascular disease