The prevalence of Fabry disease in a Turkish population with chronic kidney patients.

BACKGROUND AND OBJECTIVES: Fabry disease (FD) is an X-linked lysosomal storage disease with various clinical symptoms due to a deficiency of an enzyme called alpha-galactosidase A. The likelihood of nephropathy increases with age and the severity of the mutation in Fabry patients. Fabry disease is difficult to diagnose. The exact incidence and prevalence of Fabry disease are unknown due to its atypical or oligosymptomatic forms. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: GLA gene mutations were examined in patients over the age of 18 who were followed up on with a diagnosis of chronic kidney disease and who had or did not receive renal replacement therapy from October 2017 to December 2019. RESULTS: A total of 18 sites in 8 locations around Turkey volunteered to participate in the study, including people aged 18 and older with stages 1-5 of chronic kidney disease (CKD) or getting renal replacement therapy. 1904 patients were screened in total. In 13 cases, a D313Y pseudo mutation in the GLA gene was discovered. GLA gene mutations were found and pathologically assessed in four of the tested cases. CONCLUSIONS: The range of clinical symptoms of Fabry disease, as well as the frequent delays in diagnosis, result in treatment being too late. We believe that screening chronic renal patients at high risk for Fabry disease is warranted.

The Effects of CNI and Mtori-Based Regimens on Bone Mineral Density After Renal Transplantation.

Background: Since glucocorticoids are used in low maintenance doses today, the relationship between calcineurin inhibitors (CNI) and osteoporosis has become clinically significant in osteoporosis after solid organ transplantation. However, there is evidence that the mammalian target of rapamycin inhibitors (mTORi) may be beneficial via osteoclast inhibition. Objective: The bone mineral density (BMD) changes are investigated in renal transplant patients under CNI or mTORi-based maintenance regimens during the first five-year post-transplant course. Methods: This study consists of thirty-three renal allograft recipients with less than one year of dialysis history. The exclusion criteria were: being older than 50 years old, history of bisphosphonate use, parathyroidectomy, CNI-mTORi switch after the post-transplant third month, diuretic use, and history of malignancy. First and fifth-year BMD scores and simultaneous laboratory parameters were evaluated. Results: CNI (n=21) and mTORi group (n=12) had similar demographics, dialysis vintages, first and fifth-year serum parathormone, calcium, phosphate, magnesium, alkaline phosphatase, and 25-OH-vitamin D levels. The femur neck scores of the CNI group decreased from -0.82 (±0.96) to -1.52 (±0.92) (p=0.020). We observed a significant decrease in the CNI group compared to the mTORi group [-0.70 (±0.68) and 0.30 (±0.36), respectively; p<0.01] when the BMD score changes were evaluated among years. The mean femur neck score of the mTORi group increased insignificantly from -1.13 (±0.65) to -0.82 (±0.56) at the fifth-year DXA scan (p=0.230). Similar trends were also observed in L1-4 scores. Conclusion: Our study suggests that CNI-based treatment is associated with decreased femur neck BMD scores, and mTORi-based treatment tends to be beneficial in the post-transplant five-year follow-up.

Factors Affecting Bone Health in Kidney Transplant Recipients: Klotho Gene Single-Nucleotide Polymorphisms and Other Clinical Features.

OBJECTIVES: Posttransplant bone diseases are a major cause of morbidity in kidney transplant recipients. We investigated the relationship between klotho gene single-nucleotide polymorphisms and bone diseases after kidney transplant. We also aimed to identify possible risk factors for development of bone disease. MATERIALS AND METHODS: The study consisted of 251 kidney transplant recipients (164 men and 87 women) with minimum follow-up of 3 years after kidney transplant. Patients with prolonged immobilization, malignancy, parathyroidectomy, glomerular filtration rates less than 30 mL/min/1.73 m², hypo- or hyperthyroidism, and treatment with drugs that affect bone metabolism were excluded. We investigated the relationship between 6 single-nucleotide polymorphisms of the klotho gene (rs480780, rs211234, rs576404, rs211235, rs9536314, and rs1207568) and development of osteoporosis, avascular bone necrosis, and persistent hyperparathyroidism. RESULTS: Longer dialysis treatment (odds ratio, 1.13; P = .002) and rs211235 single-nucleotide polymorphism in the klotho gene (odds ratio, 9.87; P = .001 for GG genotype) were significantly associated with persistent hyperparathyroidism. A higher magnesium level was detected as a protective factor from development of persistent hyperparathyroidism (odds ratio, 0.19; P = .009). Persistent hyperparathyroidism was defined as a risk factor for development of osteopenia/osteoporosis (odds ratio, 2.76; P = .003) and avascular bone necrosis (odds ratio, 2.52; P = .03). Although the rs480780 (odds ratio, 8.73; P = .04) single-nucleotide polymorphism in the klotho gene was defined as a risk factor for development of osteopenia/osteoporosis, none of the klotho single-nucleotide polymorphisms was found to be associated with development of avascular bone necrosis. CONCLUSIONS: Persistent hyperparathyroidism could be an important indicator for development of bone disease in kidney transplant recipients. Also, some of the klotho gene single-nucleotide polymorphisms are associated with higher risk for bone disease after kidney transplant.

Kidney biopsy in the elderly: diagnostic adequacy and yield.

PURPOSE: The number of kidney biopsies (KB) performed in elderly patients has been increasing. Safety and usefulness of elderly KB have been well established, whereas much less is known about diagnostic adequacy and yield in this patient population. METHODS: We performed a retrospective study of KBs in 428 patients from April 2015 to December 2017 at an academic institution. We compared KB from 50 patients aged over 64 (elderly) with KB from 378 patients aged between 18 and 64. RESULTS: Gender ratio, body mass index, systolic and diastolic BP, creatinine values, incidences of AKI at the time of biopsy, INR/aptt values, and platelets were similar between the two groups. eGFR and number of transplant biopsies were lower in the elderly biopsy group. The glomerular yield was similar between the two groups (22 ± 14 vs. 22 ± 13, p = 0.869). The likelihood of obtaining more than ten glomeruli was 87% and 88%, respectively, without a significant difference. Inadequate samples were encountered in 6% of the elderly and 5.6% of the non-elderly KB, again without a significant difference. Samples taken by nephrologist had higher glomerular yield for both groups (25 ± 13 vs. 18 ± 12 overall, 26 ± 14 vs. 18 ± 14 for elderly, p < 0.001 both). Inadequate biopsies were lower in the nephrologist group when all patients were considered (3% vs. 9%, p = 0.025). Results were numerically similar for the elderly patients, but the difference was not statistically significant (2% vs. 8%, p = 0.322). No deaths occurred in both arms. Minor complications were not different for each group (4.5% vs. 4%). There were no major complications in elderly patients. However, the difference did not reach statistical significance. CONCLUSION: The world is aging, leading to an increased number of KB in older patients. KB in the elderly is a safe, effective, and an indispensable tool for the nephrologist. This study suggests there is no need to fear lower diagnostic adequacy in the decision making of a KB for an elderly patient.

Association between calcitriol and paricalcitol with oxidative stress in patients with hemodialysis.

Background: The pathophysiological basis of chronic kidney disease and its complications, including cardiovascular disease, are associated with chronic inflammation and oxidative stress. We investigated the effects of active vitamin D (calcitriol) and synthetic vitamin D analog (paricalcitol) on oxidative stress in hemodialysis patients. Methods: This cross-sectional study was composed of 83 patients with a minimum hemodialysis vintage of one year. Patients with a history of any infection, malignancy, and chronic inflammatory disease were excluded. Oxidative markers (total oxidant and antioxidant status) and inflammation markers (C-reactive protein and interleukin-6) were analyzed. Results: A total of 47% (39/83) patients were using active or analog vitamin D. Total antioxidant status was significantly higher in patients with using active or analog vitamin D than those who did not use (p = 0.006). Whereas, total oxidant status and oxidative stress index were significantly higher in patients with not using vitamin D when compared with the patients who were using vitamin D preparation (p = 0.005 and p = 0.004, respectively). On the other hand, total antioxidant status, total oxidant status, and oxidative stress index were similar between patients who used active vitamin D or vitamin D analog (p = 0.6; p = 0.4 and p = 0.7, respectively). Conclusion: The use of active or selective vitamin D analog in these patients decreases total oxidant status and increases total antioxidant status. Also, paricalcitol is as effective as calcitriol in decreasing total oxidant status and increasing total antioxidant status in patients with chronic kidney disease.

Combining clinical features and MEST-C score in IgA nephropathy may be a better determinant of kidney survival.

Introduction. IgA nephropathy (IgAN) is a heterogeneous disease with highly variable clinical and histopathological features. We investigated the effects of Oxford classification and clinical features on renal survival in patients with IgAN.Methods. This retrospective observational study conducted from 2013 to 2017. Ninety-seven patients who were followed up more than six months were examined.Results. A total of 97 patients (68% male and median age 40 years) were enrolled in this study. 13% of patients developed end stage renal disease (ESRD) within the median of 37 months of follow-up. Need for renal replacement therapy at the time of diagnosis, serum creatinine level of higher than 1.97 mg/dl, serum albumin level less than 3.5 gr/dl, 24-hour urine protein level of higher than > 3.5 g/day, the percentage of glomerulosclerosis higher than 53%, T2 score and total MEST-C score higher than two were found to be significant predictors of development of ESRD. None of the clinical or histopathological features were found to be significant predictor of steroid treatment sensitivity except T1-2 scores.Conclusion. We think that IgA nephropathy is a heterogeneous disease that requires clinical and histopathological features to be evaluated together, but not individually, to determine renal survival.What is new. Iga nephropathy is a heterogeneous disease and modern pathologic classification systems is not enough to predict to prognosis. Histopathological features to be evaluated with clinical features, but not individually, to determine renal survival. Also glucocorticoid treatment response seems to be independent from clinical and histopathological features except T1-2 score.

Evaluation of Clinical, Laboratory and Treatment Modalities in C3 Glomerulopathy: Single Center Experience.

BACKGROUND/AIM: C3 glomerulopathy (C3GP) defines a rare group of glomerulonephritis (GN), which could lead to end stage renal disease (ESRD). Histopathologic features of the disease have yet to be defined and the prognostic factors and optimal treatment are not fully known. The purpose of this study was to determine the demographic, histological change, treatment modalities and outcomes among patients with C3GP. MATERIAL AND METHOD: This retrospective observational study was conducted in the Department of Nephrology, Gazi University, Ankara, from 2013 to 2017. All patients with kidney biopsies fulfilling the criteria for C3GP were included in the study. RESULTS: Twenty-four patients with C3GP (50% male and of middle age - 43 years old) were enrolled in this study. 21% (5/24) patients developed ESRD. Renal biopsy findings such as crescent formation, glomerulo-sclerosis and tubular atrophy were similar in patients with ESRD, when compared to patients who did not develop ESRD. The treatment modalities of the patients were examined in two groups as MMF based and non-MMF based. The difference in the preservation of eGFR did not reach statistical significance between these two groups. The success rate of complete remission was similar between both groups. Serum creatinine levels >2.3 mg/dl at admission and need for renal replacement treatment (RRT) were associated with decreased renal survival. CONCLUSION: MMF based or non-MMF based treatments have similar efficacy in C3GP. Serum creatinine level higher than 2.3 mg/dl at the time of diagnosis and need for RRT during admission are a strong predictor of ESRD with high sensitivity and specificity.

Prognostic factors in glomerular diseases with crescents.

INTRODUCTION: More than 50% of glomerular crescent formation is required for a diagnosis of crescentic glomerulonephritis in a kidney biopsy. Although treatment protocols have been established for diffuse crescentic glomerulonephritis, there is no standard treatment for patients with fewer crescents in renal biopsies. In this study the importance of crescent percentage and clinical features on renal survival independent of underlying disease was investigated. METHODS: This retrospective observational study was conducted between 2013 and 2017. Forty-nine patients with crescent formation in their kidney biopsies were evaluated. We compared clinicopathological features and renal survival. We evaluated the factors affecting the course of end stage renal disease (ESRD). RESULTS: A total of 49 patients (57% male and median age 49 years) were enrolled in this study. 39% of patients developed ESRD at follow-up. Logistic regression analysis showed that the requirement for renal replacement treatment on admission (p < 0.001), serum creatinine level above 2.7 mg/dL (p < 0.001), the presence of more than 50% glomerulosclerosis (p = 0.04) and more than 34% crescent formation (p = 0.002) were significantly associated with ESRD. Kaplan-Meier survival analysis revealed that patients with less than 34% crescent in kidney biopsy and a serum creatinine level less than 2.7 mg/dL had increased kidney survival (log-rank test p: 0.01 and p: 0.002). CONCLUSION: Patients with crescent formation in kidney biopsy more than 34% should be evaluated for more aggressive treatment modalities regardless of the underlying disease, especially if the serum creatinine level is above 2.7 mg/dL.

Coeliac crisis mimicking nephrotic syndrome in a post-partum patient.

BACKGROUND: Coeliac crisis is a life-threatening presentation of coeliac disease. Severe diarrhoea, weight loss, electrolyte imbalances and malnutrition are prominent features. Although mainly a disease of childhood, it can on the rare occasion be diagnosed in adults. CASE PRESENTATION: A 25-year-old female with severe generalised oedema, lower extremity weakness, hypokalemia and profound hypoalbuminemia was referred with an initial diagnosis of nephrotic syndrome. Three months previously she had given birth to a healthy child following an uneventful pregnancy. She did not have proteinuria. She had a history of diarrhoea with gluten-containing food since childhood but lacked a formal diagnosis of coeliac disease. A duodenal biopsy confirmed the suspected diagnosis. Coeliac crisis was diagnosed with life-threatening multisystem involvement. Introduction of a gluten-free diet abolished all disease symptoms and ameliorated laboratory parameters at six months' follow-up. CONCLUSION: Coeliac crisis is a rare, yet dangerous presentation of coeliac disease in adults. As this case suggests, it can present with generalised oedema and hypoalbuminemia mimicking nephrotic syndrome. Rapid diagnosis is the key to successful treatment.

Hypothalamic Energy Regulatory Peptides in Chronic Kidney Disease.

Loss of appetite affects one-third of patients with CKD and is the leading cause of malnutrition in this population. Orexigenic Agouti-related peptide (AgRP) with neuropeptide-Y (NPY) and anorexigenic melanocyte-stimulating hormone-α (MSH-α) with cocaine- and amphetamine-regulated transcript (CART) are known to regulate appetite. In this study, we aimed to evaluate the levels of these peptides in CKD patients compared to healthy subjects and demonstrate the effects of dialysis treatment and erythropoiesis-stimulating agent (ESA) therapy. The cross-sectional study is composed of consecutive inclusion of 20 healthy individuals, 20 predialysis CKD patients, 20 HD, and 20 peritoneal dialysis (PD) patients. Exclusion criteria were an active infection, history of malignancy, hypo- or hyperthyroidism, and diabetes. Patients on dialysis had targeted Kt/Vs. Demographic features and BMIs of the four groups were similar. Levels of AgRP, NPY, AMSH, and CART were significantly different between groups. Nondialysis CKD patients had significantly lower hypothalamic hormones compared to healthy individuals, HD and PD patients (P = 0.02, P = 0.03, and P = 0.07 for AgRP; P = 0.02, P = 0.01, and P = 0.09 for NPY; P = 0.02, P = 0.02, and P = 0.03 for AMSH; P = 0.02, P = 0.005, and P = 0.030 for CART). Dialysis patients with or without ESA treatment had similar hormone levels (P = 0.13 for AgRP; P = 0.11 for NPY; P = 0.23 for AMSH, and P = 019 for CART). Predialysis CKD patients have lower orexigenic and presumably indirectly lower anorexigenic peptides compared to healthy subjects and dialysis patients. ESA treatment does not affect these hypothalamic peptides in dialysis patients.