Analysis of Prevalence and Trends in the Biopsy-Proven Native Kidney Diseases in Iranian Population: A 12-year Survey from a Referral Center.

Background & Objective: The prevalence of glomerular diseases, as the leading cause of chronic kidney disease, is increasing. Renal biopsy is still the gold standard for diagnosis of the most kidney disorders. Data on prevalence of the biopsy-proven kidney diseases in Iran is limited and none of the previously reported studies used electron microscopic (EM) evaluation for the diagnosis. This study was conducted to analyze the prevalence of biopsy-proven kidney diseases in a referral center in Iran. Methods: The reports of kidney biopsy samples from 2006 to 2018 referred to a pathology center, affiliated with Tehran University of Medical Sciences were reviewed. The prevalence of different disorders was assessed based on the clinical presentation in 3 age categories, including childhood, adulthood, and elderly. Results: Among 3455 samples, 2975 were analyzed after excluding transplant-related specimens, suboptimal specimens, and those with uncertain diagnoses. Nephrotic syndrome (NS) (39%) was the most common cause of biopsy followed by subnephrotic proteinuria (18%), hematuria in association with proteinuria (15%), renal failure (9%), isolated hematuria (6%), lupus (4%) and the other non-specific manifestations such as hypertetion or malaise (each one less than 2%). The most common diagnoses included membranous nephropathy (MGN) (17.9%), focal segmental glomerulosclerosis (FSGS) (15.9%), lupus nephritis (LN) (13.7%), minimal histopathological findings (unsampled FSGS versus Minimal Change Disease, 12.1%), Immunoglobulin-A (IgA) nephropathy (6.5%) and Alport syndrome (6.1%). MGN was the most frequent disease before 2013, but FSGS became more frequent after that. Conclusion: NS and proteinuria were the most indications for kidney biopsy. Although MGN was the most common disease, the prevalence of FSGS has been increasing in recent years and making it the most common disease after 2013. LN and IgA nephropathy are the most common causes of secondary and primary GN presenting with proteinuria and hematuria, respectively.

Spectrum and Distribution of Biopsy-proven Kidney Diseases: A 12-year Survey of a Single Center in Iran.

Data about the prevalence of biopsy-proven kidney diseases in Iran are rare, and none of the previous studies used electron microscopy for diagnosis. This study aimed to analyze the prevalence of biopsy-proven kidney diseases in Iran's primary referral center. To the best of our knowledge, this is the most extensive study carried out in Iran. Reports of kidney biopsy samples from patients referred to our center in 2007-2018 were reviewed for demographic data, clinical presentation, and final diagnosis. Statistical analyses were performed. Among the 3455 samples received, 2975 were analyzed. Nephrotic syndrome (39%) was the most common cause of biopsy, followed by subnephrotic proteinuria (18%), hematuria in association with proteinuria (15%), renal failure (9%), isolated hematuria (6%), and lupus nephritis (LN) (4%). The most common diagnoses were membranous glomerulonephritis (17.9%), focal segmental glomerulosclerosis (FSGS) (15.9%), LN (13.7%), minimal histopathological findings (unsampled FSGS vs. minimal change disease, 12.1%), Immunoglobin A nephropathy (IgAN) (6.5%) and Alport syndrome (6.1%). NS and proteinuria were the most common indications for a kidney biopsy. IgAN and LN were the most common causes of primary and secondary glomerulonephritis, presenting with hematuria and proteinuria, respectively. Although membranous glomerulonephritis was the most common disease, it has been replaced by FSGS in recent years.

Expression of Programmed Cell Death 1 and Helios Genes Correlates With rs872071A>G and rs12203592C>T Single-Nucleotide Polymorphisms of InterferonRegulatory Factor 4 in Patients with T-Cell-Mediated Rejection of Renal Allograft.

OBJECTIVES: Acute T-cell-mediated rejection of the renal allograft is a serious posttransplant challenge that requires administration of high-dose immunosuppressive drugs with considerable side effects; therefore, specific targeting of T-cell responses may improve both prevention and treatment of T-cell-mediated rejection. A potential candidate for this purpose is interferon regulatory factor 4 because of its implication in differentiation and function of T cells. Our aim was to evaluate the frequency of the rs872071A>G and rs12203592C>T single-nucleotide polymorphisms of the interferon regulatory factor 4 gene and association of these 2 polymorphisms with the gene expression of programmed cell death 1 and Helios in patients with T-cell-mediated rejection versus stable recipients. MATERIALS AND METHODS: Sixty recipients with T-cell- mediated rejection and 60 age-matched and sex-matched stable recipients were recruited. Two single-nucleotide polymorphisms of interferon regulatory factor 4 gene, as well as the expression of programmed cell death 1 and Helios genes in peripheral blood mononuclear cells, were investigated with real-time polymerase chain reaction. RESULTS: Programmed cell death 1 gene expression was reduced in patients with T-cell-mediated rejection versus stable recipients (P = .03). The frequency of rs872071A>G and rs12203592C>T single-nucleotide polymorphisms showed no significant difference between groups. Presence of the rs12203592C>T single-nucleotide polymorphism was directly correlated with the expression of programmed cell death 1 gene (P = .049), and rs872071A>G positivity was directly correlated with Helios gene expression (P = .008), which suggests an inhibitory role for interferon regulatory factor 4 on programmed cell death 1 and Helios molecules. CONCLUSIONS: Programmed cell death 1 gene expression was lower in patients with T-cell-mediated rejection versus stable recipients. Low-expressing singlenucleotide polymorphisms of interferon regulatory factor 4 could enhance the downstream gene expression of programmed cell death 1 and Helios immunoregulatory molecules. Therefore, specific inhibition of interferon regulatory factor 4 may promote tolerance induction in the allograft.

Comparing IRF-4 Gene Expression Between Acute T cell- Mediated Rejection and Stable Renal Transplant Recipients.

INTRODUCTION: Renal transplant rejection is one of the clinical challenges, which usually requires administration of immunosuppressive drugs causing serious side effects. Therefore, invention of effective and specific therapeutics is necessary to control undesired immune responses particularly T-cell reactions to allograft. Interferon Regulatory Factor-4 (IRF-4) due to its implication on T cells differentiation and function might be targeted to treat T cell-mediated cellular rejection (TCMR). The aim of this study was to investigate the association between IRF-4 gene expression and acute TCMR, as well as to examine the correlation between IRF-4 gene expression and cellular expression of Programmed cell death-1 (PD-1) and Helios molecules. METHODS: Peripheral blood samples were obtained from 30 patients with biopsy proven acute TCMR and 30 stable recipients. IRF-4 gene expression was quantified using RT-PCR, and cellular expression of PD-1 and Helios were evaluated with flowcytometry. RESULTS: IRF-4 gene expression was significantly increased in acute TCMR patients compared with stable recipients (P < .05). Helios protein expression was slightly decreased in TCMR group but this was not statistically significant. There was a negative correlation between IRF-4 gene expression and PD-1 as well as Helios frequency in the whole studied population. CONCLUSION: IRF-4 expression increases in acute TCMR which might also lead to a diminished expression of downstream immunoregulatory molecules such as PD-1 and Helios. Therefore, specific inhibition of IRF-4 may be helpful in managing acute TCMR.

Association Between Pre-Transplant Magnesemia and Post-Transplant Dysglycemia in Kidney Transplant Recipients.

BACKGROUND: Serum magnesium (Mg) status in kidney transplant recipients has been a center of attention in the past few years. Current evidence suggests an association between pre-transplant hypomagnesemia and post-transplant hyperglycemia. OBJECTIVE: The purpose of this study was to assess the associations of pre-transplant magnesemia with blood glucose disturbances within 6 months post-kidney transplantation. METHODS: In this retrospective cohort, 89 first-time kidney transplant recipients with 6 months of follow-up were included. None of the participants had a positive history of rejection, pre-transplant history of diabetes mellitus or fasting plasma glucose ≥ 100 mg/dL. RESULTS: Post-transplant diabetes mellitus (PTDM) and impaired fasting glucose (IFG) 6 months post-transplant was found in 7.9% and 41.6% of the study group, respectively. The mean pre-transplant serum Mg level was 1.92 ± 0.30 mg/dL in the study population (n = 89), and it was significantly lower in IFG (n = 37) and IFG/PTDM (n = 44) groups compared to normoglycemic (n = 45) recipients (1.83 ± 0.31 mg/dL vs. 2.00 ± 0.27 mg/dL, P = 0.008, and 1.84 ± 0.31 mg/dL vs. 2.00 ± 0.27 mg/dL, P = 0.012, respectively). Patients with serum Mg less than 1.9 mg/dL were nearly 2.6 times more likely to develop IFG or IFG/PTDM within 6 months post-transplant (P = 0.044 and P = 0.040, respectively). CONCLUSIONS: Pre-transplant hypomagnesemia may be considered a risk factor for developing post-transplant glycemic disturbances, and patients with lower pre-transplant Mg concentration could be at a higher risk for developing IFG.

Comparing the Effect of Immediate versus Delayed Initiation of Tacrolimus on Delayed Graft Function in Kidney Transplant Recipients: A Randomized Open-label Clinical Trial.

OBJECTIVE: Delayed graft function (DGF) is an early complication after kidney transplantation with negative impact on allograft outcomes. This study assessed the effect of delayed initiation of tacrolimus as a nephrotoxic drug, on DGF occurrence and allograft function. METHODS: This randomized, open-label clinical trial was conducted on kidney transplant recipients with the age of at least 14 years who underwent the first kidney transplantation from deceased or living donor. Patients were randomly allocated to immediate (n = 26) or delayed tacrolimus (n = 27) groups. All patients received thymoglobulin as induction therapy and similar maintenance immunosuppression including tacrolimus, mycophenolate, and prednisolone with the difference in the time of initiation of tacrolimus either on the day of transplantation (immediate tacrolimus group) or day 3 after transplant (delayed tacrolimus group). FINDINGS: DGF incidence (46.15% vs. 37.04%; P = 0.501) and duration (9.75 ± 6.41 vs. 8.6 ± 6.16 days; P = 0.675) were not different between the immediate and delayed tacrolimus groups. Estimated creatinine clearance using Cockcroft-Gault equation (63.14 ± 18.81 vs. 58.19 ± 19.42 mL/min in immediate and delayed tacrolimus groups respectively; P = 0.373) and estimated acute rejection-free survival were also comparable between the groups over the 3 months of follow-up. Compared with the immediate group, the delayed tacrolimus group showed higher estimated 3-month grafts' survival (100% vs. 84.27%; P = 0.072). CONCLUSION: Delayed initiation of tacrolimus after kidney transplantation under the umbrella of thymoglobulin induction did not result in either lower incidence or duration of DGF or improved the level of graft function in kidney transplant recipients but non-statistically significant increased 3-month grafts' survival.