The Renal Histopathological Findings in Patients with Renal Allograft Dysfunction: A Retrospective Single Center Study.

INTRODUCTION: Despite many advances in the development of knowledge and application of new immunosuppressive medications over the past two decades, the improvement has only been seen in the short-term outcome of kidney transplantation while the long-term survival of kidney transplantation has not significantly improved. Allograft kidney biopsy may help to determine the causes of allograft dysfunction which may change the treatment strategy. METHODS: In this retrospective study, kidney transplant recipients who underwent kidney biopsy in Shariati hospital during the years 2004 to 2015, at least three months after the kidney transplantation, were included for evaluation. Chi-square, ANOVA, post-hoc LSD, and T-test were used for data analysis. RESULTS: A total number of 525 renal transplant biopsies were performed; 300 of them had complete medical records. The reported pathologies consisted of acute T-Cell mediated rejection (TCMR) (17%), interstitial fibrosis and tubular atrophy/chronic allograft nephropathy (IFTA/CAN) (15%), calcineurin inhibitor (CNI) nephrotoxicity (12.8%), borderline changes (10.3%), glomerulonephritis (GN) (8.9%), antibody mediated rejection (ABMR) (6.7%), transplant glomerulopathy (TG) (5.3%), normal (8.4%), and other pathologies (15.6%). C4d was positive in 19.9% of the biopsies. The pathology category had a significant correlation with allograft function (P < .001), but it had no significant relationship with age and gender of the recipient, donor and donor source (P > .05). Moreover, in about 50% of cases, treatment interventions were based on pathological results, which were effective in 77% of cases. The two-year graft and patient survival after kidney biopsy were 89% and 98%, respectively. CONCLUSION: Acute TCMR, IFTA/CAN, CNI nephrotoxicity were the most common causes of allograft dysfunction based on the transplanted kidney biopsy. In addition, pathologic reports were helpful for proper treatment.  DOI: 10.52547/ijkd.7256.

Percutaneous biopsy of kidney; comparison between prone position and sitting position.

INTRODUCTION: Percutaneous kidney biopsy has been established as a safe, reliable and minimally invasive method. This study aims to describe the author's experience with biopsy of the kidney and to compare the results in sitting position versus prone in terms of the complication rate. MATERIALS AND METHODS: Patients were divided into two groups: prone and sitting position according to the clinician's and patient's preference. Followed by kidney biopsy, a questionnaire was completed. Then, data and the mean number of glomeruli in each group were compared. RESULTS: Apart from sweat, presumably due to the prone position, no significant differences were found regarding the side effects including dizziness, seizure, nausea, and vomiting between the two groups. The number of glomeruli was not significantly different between two groups. CONCLUSION: In comparison with the prone position, kidney biopsy at sitting position is more comfortable at least for patients who seems couldn't tolerate prone position. We recommend sitting position for kidney biopsy owing to the low side effects rate of this diagnostic technique.

Vitamin D Supplementation and Risk of Hypercalciuria in Stone Formers.

INTRODUCTION: Whether administrating of vitamin D supplements increases the risk of hypercalciuria is still unanswered. The aim of the present study was to determine whether use of vitamin D supplementation might increase the risk of hypercalciuria. METHODS AND MATERIALS: This interventional study was conducted on 30 who suffered from vitamin D insufficiency and deficiency and also had a history of nephrolithiasis. The patients were treated with vitamin D supplement (50000 units per week for 2 months and then every 2 weeks until the end of the 3rd month). Serum and urinary biomarkers were measured at baseline and 3 months after start of vitamin D therapy. RESULTS: Administrating vitamin D supplement for 3 months led to a significant increase in serum level of 25-hydroxyvitamin D from 10.4 ± 4.2 ng/mL to 44.0 ± 10.7 ng/mL (P < .001). Also, the median level of serum parathyroid hormone was significantly reduced from 53 ng/L (interquartile range, 22 ng/L to 163 ng/L) to 38 ng/L (interquartile range, 16 ng/L to 102 ng/L; P < .001). There was also a significant increase in urinary citrate after using vitamin D supplement compared with the baseline from 341 mg (interquartile range, 90 mg to 757 mg) to 411 mg (interquartile range, 115 mg to 1295 mg; P = .045). Comparing biochemical parameters between the groups who developed 15% and greater and less than 15% increase in urinary calcium showed no significant difference after treatment. CONCLUSIONS: The use of vitamin D supplements in conventional dose in patients with vitamin D deficiency may not lead to increased risk of hypercalciuria.

Association between low bone mass and the serum RANKL and OPG in patients with nephrolithiasis.

BACKGROUND: Nephrolithiasis is a risk factor for Osteopenia and osteoporosis. Receptor activator of nuclear factor kappaB ligand (RANKL) and osteoprotegerin (OPG) regulate bone remodeling and osteoclastogenesis. This study aimed to evaluate the relation between serum OPG, RANKL concentration, and bone mineral density (BMD) in patients with kidney stone disease. METHODS: Forty-four nephrolithiasis patients with either low bone mass or normal BMD (considered control group) were enrolled in this study. BMD was measured at lumbar spine (L1-L4) and femoral neck by dual-energy X-ray absorptiometry (DEXA). The serum OPG and RANKL were determined using the ELISA method. RESULTS: The median levels of serum OPG were significantly higher in nephrolithiasis patients with low bone mass compared to the nephrolithiasis patients with normal BMD (3.9 pmol/l versus 3.1 pmol/l; P = 0.03), respectively. Negative correlation was detected between bone densities of femoral neck and OPG in patients with nephrolithiasis (r = -.0344, P = 0.02). CONCLUSION: The present study showed that high serum fasting OPG levels may be indicative of femoral neck BMD in patients with nephrolithiasis.

Action plan for determining and monitoring the prevalence of chronic kidney disease.

Chronic kidney disease (CKD) continues to remain high globally, up to 13.4% by one estimate. Although the number, geographic distribution, size, and quality of the studies examining CKD prevalence and incidence have increased over the past decade, the global capacity for CKD surveillance is still far less developed than that for hypertension, diabetes, and cardiovascular disease. Estimating CKD prevalence is constrained by inadequate standardization of serum creatinine and urine albumin assays, heterogeneity in study designs, lack of national registries in many countries, incomplete adoption of disease classification guidelines, and inconsistent use of evidence-based equations for estimating glomerular filtration rate. Goal 1: Improve monitoring of CKD prevalence. To achieve this, disseminate the rationale for CKD prevalence monitoring, achieve uniform measurement of CKD markers, promote inclusion of CKD measurements in all large chronic disease cohorts and health surveys, harness administrative claims data for CKD surveillance, and incorporate the new CKD classification system in the International Classification of Diseases. Goal 2: Improve CKD monitoring of populations underrepresented in studies to date. To achieve this, establish registries of chronic dialysis and transplantation in all countries; establish registries for special CKD groups, such as children, patients with rare diseases, and patients with special etiologies of CKD. Goal 3: Improve identification of individuals with CKD. To achieve this, implement the Kidney Disease: Improving Global Outcomes guidelines for screening and testing, carry out randomized studies on screening strategies, ensure that estimated glomerular filtration rate is reported with all reports of serum creatinine, and leverage new software for identification and follow-up of CKD cases.

The establishment and validation of novel therapeutic targets to retard progression of chronic kidney disease.

The focus of this article is to define goals and resulting action plans that can be collectively embraced by interested stakeholders to facilitate new therapeutic approaches to mitigate chronic kidney disease progression. The specific goals include identifying druggable targets, increasing the capacity for preclinical and early clinical development, broadening the availability of new therapeutic approaches, and increasing investment in the development of new therapies to limit chronic kidney disease. Key deliverables include the establishment of new regional, national, and global consortia; development of clinical trial networks; and creation of programs to support the temporary mutual movement of scientists between academia and the biotechnology and pharmaceutical sector. Other deliverables include cataloging and maintaining up-to-date records to collate progress in renal research and development, inventorying the capacity of research and clinical networks, and describing methods to ensure novel drug development.

Association of Brain-dead Donor's Urine Neutrophil Gelatinase-associated Lipocalin Levels With Kidney Allograft Function.

INTRODUCTION: Development of delayed graft function is more prevalent in patients receiving a kidney allograft from brain-dead than living donors. This study aimed to evaluate the association between urine neutrophil gelatinase-associated lipocalin (NGAL) levels in brain-dead donors and subsequent allograft function. MATERIALS AND METHODS: Urine NGAL concentration was measured in urine samples obtained from 24 brain-dead kidney allograft donors before organ retrieval. The 24 kidney recipients were followed for 6 months. The immunosuppressive therapy was similar for all of the recipients. Following transplantation, plasma creatinine was recorded daily during the recipient's stay in the hospital and then at 1, 3, and 6 months after transplantation. Delayed graft function was defined as the need for dialysis in the first 7 days after transplantation. RESULTS: The mean age of the donors was 28.7 ± 11.2 years and 70.8% were men. Their median urine NGAL level was 7.4 ng/ml (range, 2 ng/mL to 45 ng/mL). Urine NGAL levels were only associated with the need for cardiopulmonary resuscitation (P = .007). On the 1st day after transplantation, 16.7% of the recipients developed delayed graft function, which was declined to 12.5% on the 2nd day and to 8.3% during the 3rd day and the following days. No significant association was observed between the donor's urine NGAL levels and graft function (P = .86). CONCLUSIONS: Our results did not show any association between urine NGAL levels and outcome of allograft function obtained from brain-dead donors. Larger studies are required to confirm this finding.

Impact of Kidney Transplantation on Biomarkers of Oxidative Stress and Inflammation.

INTRODUCTION: Hemodialysis patients face oxidative stress and inflammation induced by both kidney dysfunction and hemodialysis procedure. These are supposed to be partly responsible for the excessive cardiovascular morbidity and mortality in hemodialysis patients. We investigated the impact of kidney transplantation on the biomarkers of oxidative stress and inflammation. MATERIALS AND METHODS: In a prospective cohort study on 32 kidney transplant candidates on hemodialysis, biomarkers of oxidative stress and inflammation were compared before and 3 months after kidney transplantation and were compared with each other as well as their values in the kidney allograft donors as the controls. These biomarkers included total antioxidant capacity, total thiol molecules, lipid peroxidation, plasma catalase, superoxide dismutase, glutathione peroxidase, and C-reactive protein. RESULTS: The mean age of the patients was 38.0 ± 15.5 years. The levels of total antioxidant capacity, total thiol molecules, and activity of glutathione peroxidase were significantly lower and the level of activity of plasma superoxide dismutase was significantly higher in the hemodialysis patients before transplantation as compared to the values for the controls and after transplantation. Lipid peroxidation was significantly higher in the patients before transplantation compared to the controls. A significantly higher level of C-reactive protein was noted in the hemodialysis patients as compared to their levels after transplantation and also C-reactive protein in the controls. CONCLUSIONS: These results suggest that oxidative stress and inflammation are elevated in hemodialysis patients which could be improved partly and significantly by restoration of kidney function after kidney transplantation.

Non-diabetic renal disease with or without diabetic nephropathy in type 2 diabetes: clinical predictors and outcome.

BACKGROUND: Renal involvement in type 2 diabetes is mostly due to diabetic nephropathy (DN), but a subset of diabetic patients could present with pure non-diabetic renal disease (NDRD) or NDRD superimposed on DN. We conducted a prospective cohort study to identify the underline renal pathology in type 2 diabetic patients with defined clinical criteria for renal biopsy. METHODS: A total of 46 patients (27 female, mean age of 48.9 ± 11.9 years) with type 2 diabetes mellitus (DM) and atypical features of DN with unexpected proteinuria, hematuria, and/or renal impairment were enrolled in this study. RESULTS: Of 46 patients with type 2 diabetes, 16 (34.8%) had DN, 20 (43.5%) had NDRD, and 10 (21.7%) had NDRD superimposed on DN. Membranous nephropathy (34%) was the most common NDRD. Patients with NDRD had a lower frequency of diabetic retinopathy (5%), shorter duration of diabetes, higher range of proteinuria, and better kidney survival. In multiple logistic regression analysis, only lack of diabetic retinopathy was independent predictor of NDRD. Positive and negative predictive value of diabetic retinopathy (DR) for diabetic nephropathy was 94 and 68%, respectively. CONCLUSION: Kidney biopsy is strongly recommended for patients with type 2 diabetes and atypical renal presentation for DN, particularly in the absence of DR. This approach could lead to diagnosis of NDRD with better renal survival.

Prospective study of BK virus infection and nephropathy during the first year after kidney transplantation.

INTRODUCTION: The aim of this study was to assess the prevalence and severity of BK virus infection, BK virus nephritis, and related risk factors among kidney transplant recipients. MATERIALS AND METHODS: BK viremia during the first year of kidney transplantation was assessed prospectively in 32 successive recipients. BK virus DNA was extracted and determined in all samples by real-time polymerase reaction assay for 1 year after kidney transplantation. RESULTS: The mean age of the patients was 33.3 ± 15.3 years. Sixteen patients (50%) received antithymocyte globulin for induction therapy. Living donor transplant consisted of 75% of the kidney donations. Maintenance immunosuppressive therapy included cyclosporine A in 27 patients (84.4%), plus tapering prednisolone and mycophenolate mofetil. BK viremia was detected in 8 patients (25%). The highest detected plasma viral load was less than 4000 copies per milliliter. BK virus was respectively positive in 5 (62.5%), 2 (25%), and 1 (12.5%) patients during the first 4, 8, and 12 months after transplantation. Biopsy-proven rejection and antirejection therapy by methylprednisolone pulses were 5 and 2.3 times more common in patients with BK virus infection (P = .01 and P = .01), respectively. CONCLUSIONS: Despite occurrence of BK virus infection in 25% of our patients, BK nephropathy did not develop in any of them. Routine screening of BK virus infection, particularly in centers with low prevalence of BK virus nephritis, may not be cost effective for predicting this disease.

The effect of treatment with N-acetylcysteine on the serum levels of C-reactive protein and interleukin-6 in patients on hemodialysis.

Patients with end-stage renal disease (ESRD) are at an increased risk of cardiovascular disease due to many factors including inflammation and oxidative stress. N-acetylcysteine (NAC) is a thiol-containing anti-oxidant with anti-inflammatory properties. We aimed to assess the effect of three months treatment with oral NAC on the plasma levels of inflammatory mediators like interleukin-6 (IL-6) and C-reactive protein (hs-CRP) in patients on hemodialysis (HD). Twenty-four patients (nine males and 15 females) on maintenance HD were recruited in the study. Their mean age was 55.3 years. All the patients received oral NAC (600 mg twice a day) for a period of three months. The serum levels of biomedical parameters and IL-6 and hs-CRP were measured at baseline and three months after initiation of treatment. A significant decrease in serum levels of hs-CRP (22.4 vs. 5.2), IL-6 (8.1 vs. 3.6), parathyroid hormone (iPTH) (257.2 vs. 158.8), ferritin (632.0 vs. 515.1) and erythrocyte sedimentation rate (ESR) (54.2 vs. 38.3) was observed following NAC treatment. Female subjects presented with a significantly higher change in serum levels of hs-CRP compared with males (23 vs. 5.4). In three subjects who were less than 40 years old, the hs-CRP and IL-6 levels showed an increase following NAC treatment. Our study found that short-term oral NAC treatment might result in the reduction of IL-6 and hs-CRP in patients who are on regular HD. This suggests that patients with ESRD may benefit from the anti-inflammatory effects of NAC.

Adaptation and implementation of the "Kidney Disease: Improving Global Outcomes (KDIGO)" guidelines for evaluation and management of mineral and bone disorders in chronic kidney disease for practice in the Middle East countries.

This review presents the views of an expert group of nephrologists from the Middle East along with an international expert on adaptation and implementation of the 2009 Kidney Disease: Improving Global Outcomes (KDIGO) guidelines for evaluation and manage-ment of mineral and bone disorders in chronic kidney disease (CKD-MBD) for practice in the Middle East countries. The members of the panel examined the KDIGO guidelines and formulated recommendations that can be implemented practically for the management of CKD-MBD in the Middle East. There was a broad agreement on most of the recommendations made by the KDIGO work-group. However, the panelists commented on specific areas and amplified certain concepts that might help the nephrologists in the Middle East. The final document was reviewed by all participants as well as by members of the Middle East task force implementation group for KDIGO guidelines. Their comments were incorporated. The guideline statements are presented along with detailed rationale and relevant discussion as well as limitations of the evidence. The panel recognized the need to upgrade the suggestion of KDIGO related to lateral abdominal radiograph and echocardiogram in patients with CKD stages 3-5D into a stronger recommendation. The panel underlined the risk of hyper-phosphatemia to CKD-MBD and the importance of prompt initiation or modification of therapy according to rising trends in para-thyroid hormone level. They recommended the use of non-calcium-based phosphate binders as the first-line therapy in CKD patients with signs of vascular calcification. The panel agreed that all aspects of the KDIGO recommendations concerning bone biopsy, evaluation and treatment of bone disease after kidney trans-plantation should be implemented as such.

Conversion to sirolimus in kidney transplant recipients: a single-center study.

INTRODUCTION: As an immunosuppressive treatment, cyclosporine carries a significant risk of nephrotoxicity. In this study, we assessed the safety and efficacy of sirolimus conversion in our kidney transplant recipients. MATERIALS AND METHODS: Sirolimus conversion in 99 kidney transplant recipients was evaluated. Serum level of creatinine, glomerular filtration rate (GFR), and the occurrence of adverse effects of sirolimus were evaluated at conversion time and 1, 6, 12, 24, and 36 months after conversion. RESULTS: The major causes of conversion were chronic allograft nephropathy and cyclosporine nephrotoxicity. The median time to conversion and follow-up were 54.7 months and 24 months, respectively. Three patients died during the study period. The acute rejection rate was 4%. In 16.6% of the patients, sirolimus was discontinued because of refractory adverse effects. No significant changes in estimated GFR and incidence of adverse effects were observed between patients with baseline estimated GFR lower or higher than 40 mL/min. Patients with early sirolimus conversion (less than 6 months after transplant) had improvement of their GFR (59.9 +/- 22.3 mL/min to 68.0 +/- 15.5 mL/min, P = .02), while kidney recipients with late conversion did not show such an improvement. The difference between GFRs in these two groups reached significant level at 12 months and stayed significant until the end of the follow-up. CONCLUSIONS: This study emphasizes that conversion of cyclosporine to sirolimus could be associated with stable kidney allograft function. However, cyclosporine discontinuation should be considered early when it is indicated.

Association of overtime urine volume and ultrafiltration changes with patient survival in continuous ambulatory peritoneal dialysis patients.

BACKGROUND: Associations between patient survival and baseline urine volume (UV), ultrafiltration (UF) volume, and combined UV and UF were evaluated in Iranian continuous ambulatory peritoneal dialysis (CAPD) patients. METHODS: From 1995 to 2006, data on 1472 CAPD patients from 26 centers were collected. Demographic, clinical, and laboratory characteristics were analyzed using STATA software. Baseline UV was considered as an indicator of residual renal function and patients with an annual decrease of more than 250 cc/day were placed in decreasing UV group. The role of a new variable, net positive fluid removal, which defines as the combination of baseline UV and UF, was also evaluated. RESULTS: Patients with higher baseline UV were significantly more married and educated and candidate for CAPD based on positive selection criteria. In dichotomous categorization, mean of serum creatinine was lower and albumin was higher in patients with UV ≥ 1000 cc/day compared with UV < 250 cc/day. A significant correlation was found between baseline UV <250 cc/day and ≥1000 cc/day and patient survival. Patients with stable UV had better survival compared with patients with decreasing UV (p = 0.04). There was no correlation between UF and patient survival. Remarkable association with patient and technique survival and net positive fluid removal ≥2000 cc/day and <500 cc/day was observed. Multiple Cox regression analysis revealed significant correlation between net positive fluid removal ≥2000 cc/day and higher patient survival [p = 0.01, hazard ratio (HR) = 13.2], higher first albumin (albumin ≥ 3.5 mg/dL, p = 0.01, HR = 0.02), and lower negative selection (p = 0.0001, HR = 11.8). CONCLUSION: Loss of UV over time and lower net positive fluid removal increase mortality of PD patients.

Chronic allograft dysfunction: major contributing factors.

Chronic, progressive, and irreversible loss of a transplanted kidney function, previously named chronic allograft nephropathy, is the leading cause of chronic allograft failure among kidney transplant recipients. Chronic allograft dysfunction (CAD) is a multifactorial process associated with progressive interstitial fibrosis and tubular atrophy. Current Data confirms that an additive series of time-dependent immunological factors such as acute and chronic antibody- and/or cell-mediated rejection and nonimmunological factors are involved in development of interstitial fibrosis and tubular atrophy as the fundamental parts of CAD. The use of calcineurin inhibitors has produced a major impact on achieving successful organ transplantation; however, although this assumption has been doubted recently, calcineurin inhibitors are deemed to be associated with nephrotoxicity and subsequent interstitial fibrosis, tubular atrophy, and kidney dysfunction. The early fibrotic changes are due to implantation stress, T-cell-mediated rejection, and infection; however, usually they do not lead to progressive fibrosis and allograft dysfunction per se. In the setting of CAD, many factors occurring lately after 1 year, such as chronic antibody-mediated rejection, recurrent or de novo glomerulonephritis, and nonadherent adequately address the existence of ongoing injuries and progression to fibrosis. Identification of patients who are at risk, close clinical monitoring, and optimization and individualization of their maintenance immunosuppressive regimen are among the means that could help us to improve the long-term outcome of kidney transplantation.