Characteristics and Sensitization Risk Factors in Kidney Transplant Wait List Candidates: Panel Reactive Antibodies Status Is Crucial for Successful Kidney Allocation Systems in Turkey.

OBJECTIVES: Kidney transplant is the treatment of choice for end-stage renal disease. Because of the insufficient supply of donor organs for transplant, the number of patients on the transplant wait list is increasing. We analyzed demographic and clinical factors including sensitization status of patients on the kidney transplant wait list in our center. MATERIALS AND METHODS: Patients on the kidney transplant wait list at Ankara University School of Medicine by July 2018 were evaluated. Data on demographics, comorbidities, treatment characteristics, and immunologic properties were collected. RESULTS: The study included 528 kidney transplant candidates whose mean time on the deceased donor organ wait list was 57 ± 47 months. Enlisted patients were aged 53 ± 13 years, and 95% of them were on dialysis. Dialysis vintage was longer and percentage of patients who had anti-HLA antibodies was higher in women than men (P = .004 and P < .001, respectively). Levels for median fluorescence intensity were higher in women compared with men (class I, P < .001; and class II, P = .011). Transfusion (P < .001), pregnancy (P = .001), transplant (P < .001), longer dialysis vintage (P = .021), and longer time on wait list (P = .001) were associated with anti-HLA antibody positivity. Multiple regression analysis revealed that a history of transplant and blood transfusion were independent risk factors of a positive panel reactive antibodies. CONCLUSIONS: In our kidney transplant candidates on the wait list, sensitization by transplant has a significant impact on development of anti-HLA antibodies. Updates of the organ allocation system to consider sensitized candidates and strategies to expand the deceased donor organ pool and donation rates are needed to increase the rate of deceased donor kidney transplant in Turkey.

Infectious Complications in Patients with Primary Glomerulonephritis over 10 Years: A Single-Center Experience in Turkey.

INTRODUCTION: Infections can play an important role in the mortality and morbidity of patients with glomerulonephritis. However, the frequency of infectious complications in primary glomerulonephritis and their burden to the healthcare managements are not clear. METHODS: We evaluated the infectious complications in patients with biopsy-proven focal segmental glomerulosclerosis, membranous glomerulonephritis, IgA nephropathy, minimal change disease, membranoproliferative glomerulonephritis, and chronic glomerulonephritis during the last 10 years in a single center. We recorded the demographic, clinical, and laboratory characteristics; treatment modalities; infectious episodes; and infection-related mortality and morbidity of the patients. RESULTS: Of the patients, 154 (63.6%) received immunosuppressive treatment and 88 (34.4%) were followed up under conservative treatment. Overall, 118 infectious episodes were noted in 64 patients, with an infection rate of 0.20 per patient-year. Total infectious complications were higher in the immunosuppressive group than in the conservative group (42.1 vs. 23.3%, p = 0.005). Infection-related hospitalizations were also higher in the immunosuppressive group (p = 0.01). The most frequently infected area was the lungs (15.7%). Although bacterial infections were the most common in both groups, 14.9% of the immunosuppressive group had cytomegalovirus (CMV) replication. Age >50 years (OR 2.19, p = 0.03), basal serum albumin <2.5 g/dL (OR 2.28, p = 0.02), cyclophosphamide (OR 2.43, p = 0.02), and cyclosporine (OR 2.30, p = 0.03) were independently associated with experiencing infectious episodes. CONCLUSIONS: Because of high seropositivity for CMV in Turkey, it might be a wise approach to use prophylactic antiviral drugs in patients treated with immunosuppressive treatments. Close monitoring of patients with primary glomerulonephritis, especially those treated with immunosuppressive therapy, is important for reducing infection-related morbidity and mortality.

NT-proBNP level in stage 3-4 chronic kidney disease and mortality in long-term follow-up: HAPPY study subgroup analysis.

OBJECTIVE: This was an investigation of the relationship between the N-terminal pro-brain natriuretic peptide (NT-proBNP) level and mortality in patients with stage 3-4 chronic kidney disease (CKD). METHODS: This study was designed as a subgroup analysis of the Heart Failure Prevalence and Predictors in Turkey (HAPPY) study. The HAPPY study included 4650 randomly selected individuals from the 7 geographical regions of Turkey. A total of 191 subjects from the original cohort with an estimated glomerular filtration rate (eGFR) <60 mL/min/1.1.73 m² were enrolled in this study and the relationship between NT-proBNP and mortality was investigated. Prognostic variables for total and cardiovascular mortality were also examined using Cox regression analysis. RESULTS: The mean length of follow-up was 76.12±22.45 months. The mean NT-proBNP level was 423.54±955.88 pg/mL. During follow-up, 51 subjects (26.7%) died from any cause and 36 subjects (18.8%) died from a cardiovascular cause. The presence of hypertension (hazard ratio [HR]: 1.89; 95% confidence interval [CI]: 1.01-3.50; p=0.048), anemia (HR: 2.49; 95% CI: 1.20-5.15; p=0.014), male gender (HR: 2.64; 95% CI: 1.44-4.86; p=0.002) and log NT-proBNP (HR: 4.93; 95% CI: 2.83-8.58; p<0.001) were independent variables for total mortality. The presence of hypertension (HR: 2.47; 95% CI: 1.09-5.56; p=0.029), male gender (HR: 2.79; 95% CI: 1.38-5.62; p=0.004), eGFR (HR: 0.94; 95% CI: 0.91-0.98; p=0.005) and log NT-proBNP (HR: 6.31; 95% CI: 3.11-12.81; p<0.001) were independent predictors of cardiovascular mortality. CONCLUSION: NT-proBNP was found to be an independent prognostic marker in patients with stage 3-4 CKD.

Fabry Disease Screening in Patients With Kidney Transplant: A Single-Center Study in Turkey.

OBJECTIVES: Fabry disease is a rare X-linked multisystemic lysosomal storage disorder of the glycosphingolipid metabolic pathway. Nephropathy is one of the most important complications of Fabry disease, and patients with classical phenotype are at risk of developing endstage kidney disease. In this study, we investigated the use of screening for Fabry disease in kidney transplant recipients at our center. MATERIALS AND METHODS: We screened 301 kidney transplant recipients with functioning grafts. Analyses for α-galactosidase A gene mutation were performed in all female and male kidney transplant recipients. We also measured leukocyte α-galactosidase A enzyme activity in patients with identified GLA mutation. RESULTS: In 301 kidney transplant recipients, mean age was 42.9 ± 12.5 years, and the number of male patients was 180 (60%). Mean time after transplant was 79 ± 56 months, and estimated glomerular filtration rate was 66.8 ± 21 mL/min/1.73 m². One male patient who was diagnosed with Fabry disease before kidney transplant was also evaluated (mutation in the α-galactosidase A gene, c.1093_1101dup [p.Tyr365_lle367dup]). In 2 female patients, p.A143T (c.427G>A) mutation of unknown significance and p.D313Y (c.937G>T) heterozygous mutation were identified; however, leukocyte ?-galactosidase A enzyme activity was normal in these patients (63.7 and 67.3 nmol/h/mg protein). In the patient diagnosed with Fabry disease, family screening revealed 4 additional affected family members. DISCUSSIONS: Although prevalence was shown to be low in our center (1/301 patients; 0.33%), screening studies in kidney transplant recipients may help to detect new patients before they develop life-threatening complications such as renal involvement.

Therapeutic Effect of Plasmapheresis and Intravenous Immunoglobulin in Recipients of Kidney Transplant With High Panel-reactive Antibody Levels: A Single-center Experience.

OBJECTIVE: High panel-reactive antibody (PRA) levels limit patients' access to kidney transplantation from potential living donor candidates and decrease renal graft survival by causing acute antibody-mediated rejection (AAMR). In this article, we report our experiences about the efficiency of plasmapheresis (PP) and intravenous immunoglobulin (IVIG) in reduction of serum PRA levels in candidates for renal transplantation and in patients with AAMR. METHODS: We examined retrospectively 47 patients with high PRA levels (18 for desensitization (DS) and 29 with AAMR) at Ankara University. The reduction in PRA class 1 and PRA class 2 levels before and after the PP, IVIG, and rituximab or eculizumab therapy were evaluated. RESULTS: In the DS group, mean reduction in PRA class I ± SD was 28.0 ± 9.10 to 22.1 ± 8.14 (P <.05), and mean reduction in PRA class II ± SD was 40.3 ± 6.89 to 32.2 ± 5.68 (P < .05). In the AAMR group; mean reduction in PRA class I ± SD was 23.9 ± 9.56 to 17.8 ± 8.64 (P > .05), and mean reduction in PRA class II ± SD was 28.1 ± 8.37 to 26.7 ± 7.96 (P > .05). In total, mean reduction in PRA class I was 25.7 ± 6.66 to 19.7 ± 6.00 (P < .01). Mean reduction in PRA class II was 33.8 ± 5.93 to 29.2 ± 4.96 (P > .05). In the DS group, 3 (16.7%) patients were treated with rituximab. In the AAMR group, 9 (31.0%) patients were treated with rituximab, and 1 (5.5%) patient received eculizimab.In the DS group, the mean follow-up period in years ± SD was 5.06 ± 3.01 and no patient had graft loss. In the AAMR group, the mean follow-up period in years was 5.06 ± 2.74 and 6 (33.3%) patients had graft loss with acute rejection. CONCLUSIONS: PP and IVIG treatment provide significant reduction in PRA levels and can be used in DS protocols.

Clinical Correlates of Ambulatory Blood Pressure Phenotypes at a Tertiary Care Hospital in Turkey.

BACKGROUND/AIMS: Hypertension and its complications are major public health issues worldwide due to their association with high cardiovascular morbidity and mortality. Despite significant progress in health, the prevalence of hypertension is increasing. Ambulatory blood pressure monitoring (ABPM) is becoming increasingly important for the management of hypertension. In this study, we aimed to investigate the clinical and laboratory correlates of ambulatory blood pressure (ABP) phenotypes at a tertiary care hospital in Turkey. METHODS: The characteristics of 1053 patients were retrospectively obtained from the hospital database. Hypertension was defined as patients with office blood pressure (BP) ≥140/90 mmHg and/or previously diagnosed hypertension and/or the use of antihypertensive medication. According to the office BP and ABPM results patients were identified namely: (1) sustained normotensive (SNT) patients (both office BP and ABPM were normal), (2) sustained hypertensive (SHT) patients (both office BP and ABPM were high), (3) masked hypertensive (MHT) patients (office BP were normal, but ABPM were high), (4) white coat hypertensive (WCHT) patients (office BP were above limits, but ABPM were normal). RESULTS: A total of 1053 patients were included to the study (female/male: 608/445 and mean age 55 ± 15 years). The mean age of patients with hypertension was significantly higher than without hypertension (p< 0.0001). Hypertension was more frequent in females (p=0.009). The rates of history of diabetes mellitus (DM), hyperlipidemia (HL), and chronic kidney disease (CKD) were higher in patients with hypertension (p< 0.0001). Among patients with hypertension (n=853, 81%), ABPM results showed that 388 (45%) of patients had SHT, 92 (11%) had MHT, and 144 (17%) had WCHT, whereas 229 (27%) had SNT. Patients with MHT were significantly older than patients with SNT (p=0.025). The prevalence of SHT was higher in men than in women, whereas the prevalence of WCHT was higher in women than in men (p< 0.0001). There was no significant difference between 4 groups with regard to body mass index (p=0.142), a history of DM (p=0.189) and smoking status (self-reported) (p=0.306). Patients with SHT had the highest prevalence of history of hypertension, HL and CKD (p< 0.0001). Among patients without hypertension, 26 (13%) of patients had MHT and none of those patients was on antihypertensive treatment. CONCLUSION: Potential usages of ABPM in Turkey may include screening of high risk individuals who have traditional cardiovascular risk factors. It also provides clinicians valuable information on abnormal ABP phenotypes. Future studies are needed to clarify the risk factors of different ABP phenotypes and to evaluate the role of ABPM on detection and control of hypertension.

Profile of renal AA amyloidosis in older and younger individuals: a single-centre experience.

OBJECTIVE: In epidemiological studies of amyloid A (AA) amyloidosis from Turkey, the most frequently cause was familial Mediterranean fever (FMF) and it occurs generally in young age population. However, there are no sufficient data regarding aetiology, clinical presentation and prognosis of renal AA amyloidosis in advanced age patients. In this study, we aimed to investigate demographic, clinical presentation, aetiology and outcomes of adults aged 60 years or older patients with biopsy-proven renal AA amyloidosis. METHODS: This is a retrospective study involving 53 patients who were diagnosed with AA amyloidosis by kidney biopsy from 2006 to 2016. In all patients, kidney biopsies were performed due to asymptomatic proteinuria, nephrotic syndrome and/or renal insufficiency. The patients were separated into two groups on the basis of age (group I: ≥60 years and group II: <60 years). Outcomes of patients in terms of the requirement of renal replacement therapy and mortality were recorded. RESULTS: In patients with group I, the causes of AA amyloidosis were as follows: FMF 16 (50%), bronchiectasis 7 (23%), chronic osteomyelitis 2 (6%), inflammatory bowel disease 2 (6%), rheumatoid arthritis 2 (6%), ankylosing spondylitis 1 (3%) and unknown aetiology 2 (6%). The underlying disorders of AA amyloidosis in group II patients were as follows: FMF 17 (81%), Behcet's disease 1 (5%) and unknown aetiology 3 (14%). No statistically significant differences were detected between two groups with regard to systolic and diastolic blood pressures, albumin, proteinuria and lipids. The combination of chronic kidney disease and nephrotic syndrome was the most common clinical presentation in group I (73%) and group II (43%) (p = .05). Compared to the group II, estimated glomerular filtration rate was significantly lower in group I at the time of kidney biopsy (p = .003). At 12-month follow-up, 61% of the group I and 33% of the group II developed end-stage kidney disease requiring dialysis, while 11% of the group I died. CONCLUSION: Our results indicated that renal AA amyloidosis is a rare disease in advanced age patients. At baseline and follow-up period, advanced age patients had worse kidney disease and outcomes.

Non-Diabetic Kidney Disease in Type 2 Diabetic Patients: Prevalence, Clinical Predictors and Outcomes.

BACKGROUND/AIMS: Diabetic kidney disease (DKD) is one of the most frequent microvascular complications of diabetes and is the leading cause of end-stage kidney disease worldwide. In patients with diabetes, non-diabetic kidney disease (NDKD) can also occur. NDKD can be either alone or superimposed with the DKD. In this study, we aimed to investigate the utility of kidney biopsy in patients with type 2 diabetes mellitus (T2DM) and the predictability of diagnosing DKD versus NDKD from clinical and laboratory data. We also evaluated the prevalence and etiology of NDKD in patients with T2DM. METHODS: We retrospectively reviewed type 2 diabetic patients who had kidney biopsy in the last 10 years for diagnosing possible NDKD in our center. In all patients kidney biopsies were performed because of atypical clinical features and biopsy samples were examined by light and immunofluorescence microscopy. Clinical parameters, laboratory workup and office blood pressures were recorded for each patient at the time of biopsy. RESULTS: Eight patients were excluded due to missing data. A total of 48 patients (female/male: 26/22 and mean age: 59±8 years) were included in the study. According to the biopsy findings, 24 (50%) patients had NDKD alone, 20 (41.7%) had DKD alone and 4 (8.3%) had coexisting DKD and NDKD. The most common NDKD diagnoses were membranous nephropathy (29.2%), tubulointerstitial nephritis (20.8%) and IgA nephropathy (12.5%). There were no significant differences in three groups with respect to the duration of diabetes, proteinuria, hematuria and glycated hemoglobin A1c levels. Diabetic retinopathy (DR) was the most significant finding, which was associated with DKD. Positive and negative predictive values of DR for DKD were 88 and 81%, respectively. CONCLUSION: This study demonstrated a high prevalence of NDKD in patients with T2DM. The absence of DR strongly predicted NDKD. Clinical decision alone can lead to wrong diagnosis and delay in appropriate therapy. Clinicians should consider the kidney biopsy more liberally when there is uncertainty on the exact etiology of the kidney disease. However, prospective multicenter studies are needed to clarify the prognosis and outcomes of patients with diabetics.

Kidney biopsy in AA amyloidosis: impact of histopathology on prognosis.

In AA amyloidosis, while kidney biopsy is widely considered for diagnosis by clinicians, there is no evidence that the detailed investigation of renal histopathology can be utilized for the prognosis and clinical outcomes. In this study, we aimed to obtain whether histopathologic findings in kidney biopsy of AA amyloidosis might have prognostic and clinical value. This is a retrospective cohort study that included 38 patients who were diagnosed with AA amyloidosis by kidney biopsy between 2005 and 2013.The kidney biopsy specimens of patients were evaluated and graded for several characteristics of histopathological lesions and their relationship with renal outcomes. Segmental amyloid deposition in the kidney biopsy was seen in 29%, global amyloid deposition in 71, diffuse involvement of glomeruli in 84.2%, focal involvement in 7%, glomerular enlargement in 53%, tubular atrophy in 75% and interstitial fibrosis in 78% of patients. Histopathologically, glomerular enlargement, interstitial fibrosis, tubular atrophy, interstitial inflammation and global amyloid deposition were significantly associated with lower estimated glomerular filtration rate (eGFR) (p = .02, p < .001, p = .001, p = .009, p = .002, respectively) in univariate analysis. In multivariate analysis, tubular atrophy was the only predictor of eGFR (p = .019 B = -20.573). In the follow-up at an average of 27 months, 18 patients developed end-stage renal disease (ESRD). Among them, global amyloid deposition was the only risk factor for the development of ESRD (p = .01, OR = 18.750, %95 CI= 2.021-173.942). This is the first study showing that the histopathological findings in kidney biopsy of AA amyloidosis might have a prognostic and clinical value for renal outcomes.

Diffuse Large B-Cell Lymphoma Presenting with Bilateral Renal Masses and Hematuria: A Case Report.

Renal involvement is most often seen in conjunction with multisystemic, disseminated lymphoma either by direct extension from a retroperitoneal mass or via hematogenous spread. Primary lymphoma of the kidney is not a common entity and it is a controversial issue on account of the absence of lymphatic tissues in the normal kidney. In this case report, we describe a 19-year-old male with hematuria, acute kidney injury, and bilateral renal masses due to massive lymphomatous infiltration of the kidneys, which was diagnosed as diffuse large B-cell non-Hodgkin lymphoma by Tru-Cut biopsy.

Urinary angiotensinogen, related factors and clinical implications in normotensive autosomal dominant polycystic kidney disease patients.

BACKGROUND: Although several lines of evidence suggest that renin angiotensin system (RAS) proteins are synthesized by cyst epithelium and dilated tubules, role of intrarenal RAS in the progression of otozomal dominant polycystic kidney disease (ADPKD) is not well known. We aimed to study the levels and clinical correlations of urinary angiotensinogen (UAGT) in normotensive ADPKD patients compared with age- and sex-matched healthy subjects. METHODS: The study included 20 normotensive ADPKD patients (F/M: 11/9) and 20 age and sex matched healthy controls (F/M: 9/11). Diagnosis of ADPKD was made based on Ravine criteria. Twenty-four hours ambulatory blood pressure monitoring (ABPM) was performed. Serum concentrations of creatinine, Na, K, uric acid, and urinary concentrations of Na, K, uric acid, creatinine, protein and albumin were measured. UAGT were measured via commercially available ELISA kit. RESULTS: ADPKD patients had higher urinary albumin:creatinine ratio (UAIb/UCrea) than healthy controls (p < 0.01). UAGT/UCrea levels significantly positively correlated with urinary protein: creatinine ratio (UPro/UCrea) (r = 0.785, p = 0.01), and UAIb/UCrea (r = 0.681, p = 0.01) in normotensive ADPKD patients. CONCLUSION: This pilot study demonstrates that UAGT levels tend to be elevated and are correlated with proteinuria and albuminuria in normotensive ADPKD patients during relatively early stages of the disease.