Background Countries with culturally accepted consanguinity provide a unique resource for the study of rare recessively inherited genetic diseases. Although hereditary hearing loss (HHL) is not uncommon, it is genetically heterogeneous, with over 85 genes causally implicated in non-syndromic hearing loss (NSHL). This heterogeneity makes many gene-specific types of NSHL exceedingly rare. We sought to define the spectrum of autosomal recessive HHL in Iran by investigating both common and rarely diagnosed deafness-causing genes. Design Using a custom targeted genomic enrichment (TGE) panel we simultaneously interrogating all known genetic causes of NSHL in a cohort of 302 GJB2-negative Iranian families. Results We established a genetic diagnosis for 67% of probands and their families, with over half of all diagnoses attributable to variants in five genes: SLC26A4, MYO15A, MYO7A, CDH23, and PCDH15. As a reflection of the power of consanguinity mapping, 26 genes were identified as causative for NSHL in the Iranian population for the first time. In total, 179 deafness-causing variants were identified in 40 genes in 201 probands, including 110 novel single nucleotide or small insertion-deletion variants and 3 novel copy number variations. Several variants represent founder mutations. Conclusion This study attests to the power of TGE and massively parallel sequencing (TGE+MPS) as a diagnostic tool for the evaluation of hearing loss in Iran, and expands on our understanding of the genetics of HHL in this country. Families negative for variants in the genes represented on this panel represent an excellent cohort for novel gene discovery.

Based on the results of this study the three common causes of ARF are acute tubular necrosis (ATN, 38%), acute glumerulonephritis (24%) and hemolytic uremic syndrome (24.1%). The overall mortality rate among our patients was 24.7%, with the highest risk group being those patients suffering from ischemic ATN. In addition, the correlation (p<0.0005) between the etiology and mortality rate was particularly high in patients with ischemic ATN. Mortality was also high (68%) in children younger than 2 years. Multiple regression models revealed that among those factors that significantly differed between the survivors and nonsurvivors, only the necessity of dialysis (p<0.0005), the use of mechanical ventilation (p=0.05) and disseminated intravascular coagulation (p=0.038) can be regarded as independent determinants of ARF prognosis in children.

Kidney transplantation is the treatment of choice for children with end-stage renal disease. In Iran, a kidney transplantation program was started in the Labfi Nejad Hospital, Tehran in 1985. From 1985 to 2003, 278 children (mean age 11.6 years, 59.7% males) received their first renal transplant. All transplants were donations from live donors (12.5% live-related donors); 30.8% of patients were preemptively transplanted. The overall 1-year patient survival rate was 92% and the 5-year survival rate 74%. The median graft survival time was 7.2 years. The rate of graft survival was 88.8% at 1 year, 77% at 3 years, 67% at 5 years, 50% at 7 years, and 43% at 10 years after transplantation. The survival rate of patients and transplants improved significantly with time (p<0.05). In patients transplanted before 1997, the 5-year graft survival was 50% and 82% in patients transplanted after 1997. At the same time intervals, the frequency of acute rejection episodes was 66.6 versus 40.8% and of chronic rejection 50.5 versus 28.7%. The outcome in children below the age of 6 years was poor. Graft survival was negatively correlated with the frequency and an early time point of acute rejection episodes. The modus of transplantation (preemptive or postdialysis) did not influence the results. In conclusion, patient and graft survival in transplanted children significantly improved with time, thus reflecting greater medical and surgical experience, new immunosuppressive drugs, and better compliance.

Macrophage migration inhibitory factor (MIF) is an important pro-inflammatory cytokine expressed at sites of inflammation. We have assessed this factor (MIF) in urinary tract infections with the aim of determining a non-invasive and sensitive method to differentiate upper and lower renal involvement. Thirty-three pediatric patients with urinary track infection (25 with acute pyelonephritis, eight with acute cystitis) and 40 healthy subjects were recruited for this prospective case-control study. Pyelonephritis was differentiated from cystitis by dimercaptosuccinic acid (DMSA) scan. Urinary MIF concentration was determined using an enzyme-linked immunosorbent assay method. The urine MIF/creatinine (Cr) ratio was significantly higher in pyelonephritis patients than in those with acute cystitis and the control group (P < 0.001). The optimal cut-point of 4.90 pg/micromol Cr for the urine MIF/Cr ratio has the potential to be a biomarker for distinguishing patients with acute pyelonephritis from those with acute cystitis. Determination of the urinary MIF was also useful in selecting the patients at risk of permanent renal damage. Of those patients with pyelonephritis, based on the DMSA scan at the time of infection, scarring on follow-up DMSA scan 9-12 months later occurred in patients with the highest urinary MIF/Cr ratios. We conclude that the urine MIF/Cr ratio is a sensitive test for differentiating acute pyelonephritis from acute cystitis and also for detecting children with acute pyelonephritis who are at a higher risk for permanent renal scars in the future.

Background: Nephropathic cystinosis is a rare inherited metabolic disorder leading to progressive renal failure and extra-renal comorbidity. The prognosis relies on early adherence to cysteamine treatment and symptomatic therapies. Developing nations [DiN] experience many challenges for management of cystinosis. The aim of this study was to assess the management characteristics in DiN compared with developed nations [DeN]. Methods: A questionnaire was sent between April 2010 and May 2011 to 87 members of the International Pediatric Nephrology Association, in 50 countries. Results: A total of 213 patients were included from 41 centres in 30 nations (109 from 17 DiN and 104 from 13 DeN). 7% of DiN patients died at a median age of 5 years whereas no death was observed in DeN. DiN patients were older at the time of diagnosis. In DiN, leukocyte cystine measurement was only available in selected cases for diagnosis but never for continuous monitoring. More patients had reached end-stage renal disease in DiN (53.2 vs. 37.9%, p = 0.03), within a shorter time of evolution (8 vs. 10 yrs., p = 0.0008). The earlier the cysteamine treatment, the better the renal outcome, since the median renal survival increased up to 16.1 [12.5−/] yrs. in patients from DeN treated before the age of 2.5 years of age (p = 0.0001). However, the renal survival was not statistically different between DeN and DiN when patients initiated cysteamine after 2.5 years of age. The number of transplantations and the time from onset of ESRD to transplantation were not different in DeN and DiN. More patients were kept under maintenance dialysis in DiN (26% vs.19%, p = 0.02); 79% of patients from DiN vs. 45% in DeN underwent peritoneal dialysis. Conclusions: Major discrepancies between DiN and DeN in the management of nephropathic cystinosis remain a current concern for many patients living in countries with limited financial resources.

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Subtle abnormalities of LV function develop early when renal insufficiency is mild to moderate. MPI, measuring by PWD and TDI, are appropriate indicators of overall LV function in young patients with CKD.

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