Biopsy-proven BK virus nephropathy in renal transplant recipients: A -multi-central study from Turkey (BK-TURK STUDY).

AIM: BK polyomavirus infection is a challenging complication of renal transplantation. The management is not standardized and is based on reports from transplantation centers' experiences, usually with small sample sizes. Therefore, we aimed to present our countrywide experience with BK virus nephropathy (BKVN) in renal transplant recipients. MATERIALS AND METHODS: Our study was carried out with the participation of 30 transplantation centers from all regions of Turkey. Only cases with allograft biopsy-proven BKVN were included in the study. RESULTS: 13,857 patients from 30 transplantation centers were screened, and 207 BK nephropathy cases were included. The mean age was 46.4 ±  13.1 years, and 146 (70.5%) patients were male. The mean time to diagnosis of BK nephropathy was 15.8 ± 22.2 months after transplantation. At diagnosis, the mean creatinine level was 1.8 ±  0.7 mg/dL, and the mean estimated glomerular filtration rate was 45.8 ± 19.6 mL/min/1.73m2 . In addition to dose reduction or discontinuation of immunosuppressive drugs, 18 patients were treated with cidofovir, 11 patients with leflunomide, 17 patients with quinolones, 15 patients with intravenous immunoglobulin (IVIG), 5 patients with cidofovir plus IVIG, and 12 patients with leflunomide plus IVIG. None of the patients receiving leflunomide or leflunomide plus IVIG had allograft loss. During follow-up, allograft loss occurred in 32 (15%) out of 207 patients with BK nephropathy. CONCLUSION: BKVN is still a frequent cause of allograft loss in kidney transplantation and is not fully elucidated. The results of our study suggest that leflunomide treatment is associated with more favorable allograft outcomes.

The renoprotective effects of taurine against diabetic nephropathy via the p38 MAPK and TGF-ß/Smad2/3 signaling pathways.

Diabetic nephropathy (DN), a severe diabetes complication, causes kidney morphological and structural changes due to extracellular matrix accumulation. This accumulation is caused mainly by oxidative stress. Semi-essential amino acid derivative taurine has powerful antioxidant and antifibrotic effects. The aim of this study was to investigate the renoprotective effects of taurine through its possible roles in oxidative stress, extracellular matrix proteins, and the signaling pathways associated with the accumulation of extracellular matrix proteins in DN rats. 29 Wistar albino rats were randomly separated into control, taurine, diabetes, and diabetes + taurine groups. Diabetes animals were injected 45 mg/kg streptozosine. Taurine is given by adding to drinking water as 1% (w/v). Urine, serum, and kidney tissue were collected from rats for biochemical and histological analysis after 12 weeks. According to the studies, taurine significantly reduces the levels of malondialdehyde (MDA), total oxidant status (TOS), and protein expression of NADPH oxidase 4 (NOX4) that increase in diabetic kidney tissue. Also, decreased superoxide dismutase (SOD) activity levels significantly increased with taurine in diabetic rats. Moreover, increased mRNA and protein levels of fibronectin decreased with taurine. The matrix metalloproteinase (MMP)-2 and MMP-9 activities and their mRNA levels increased significantly, and this increase was significantly summed with taurine. There was a decrease in mRNA expression of Extracellular matrix metalloproteinase inducer (EMMPRIN). Taurine significantly increased this decrease. Diabetes increased mRNA expressions of transforming growth factor (TGF)-ß and Smad2/3. Taurine significantly reduced this induction. TGF-ß protein expression, p38, and Smad2/3 activations were also inhibited, but taurine was suppressed significantly. All these findings indicate that taurine may be an effective practical strategy to prevent renal diabetic injury.

Clinical and pathologic features of primary membranous nephropathy in Turkey: a multicenter study by the Turkish Society of Nephrology Glomerular Diseases Working Group.

BACKGROUND: We aimed to evaluate the features of primary membranous nephropathy (MNP) in Turkish people. METHODS: This is a retrospective analysis of patients with biopsy-proven primary MNP. We obtained the data collected between 2009 and 2019 in the primary glomerulonephritis registry of the Turkish Society of Nephrology Glomerular Diseases Study Group (TSN-GOLD). Patients with a secondary cause for MNP were excluded. Clinical, demographic, laboratory, and histopathological findings were analyzed. RESULTS: A total of 995 patients with primary MNP were included in the analyses. Males constituted the majority (58.8%). The mean age was 48.4 ± 13.9 years. The most common presentation was the presence of nephrotic syndrome (81.7%) and sub nephrotic proteinuria (10.3%). Microscopic hematuria was detected in one-third of patients. The median estimated glomerular filtration rate (eGFR) was 100.6 mL/min/1.73 m2 (IQR, 75.4-116.3), and median proteinuria was 6000 mg/d (IQR, 3656-9457). Serum C3 and C4 complement levels were decreased in 3.7 and 1.7% of patients, respectively. Twenty-four (2.4%) patients had glomerular crescents in their kidney biopsy samples. Basal membrane thickening was detected in 93.8% of cases under light microscopy. Mesangial proliferation and interstitial inflammation were evident in 32.8 and 55.9% of the patients, respectively. The most commonly detected depositions were IgG (93%), C3 complement (68.8%), and kappa and lambda immunoglobulin light chains (70%). Although renal functions were normal at presentation, vascular, interstitial, and glomerular findings were more prominent on biopsy in hypertensive patients. No significant effect of BMI on biopsy findings was observed. CONCLUSIONS: Despite some atypical findings, the main features of primary MNP in Turkey were similar to the published literature. This is the largest MNP study to date conducted in Turkish people.

Epidemiological features of primary glomerular disease in Turkey: a multicenter study by the Turkish Society of Nephrology Glomerular Diseases Working Group.

BACKGROUND: The largest data on the epidemiology of primary glomerular diseases (PGDs) are obtained from the databases of countries or centers. Here, we present the extended results of the Primary Glomerular Diseases Study of the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD) Working Group. METHODS: Data of patients who underwent renal biopsy and received the diagnosis of PGD were recorded in the database prepared for the study. A total of 4399 patients from 47 centers were evaluated between May 2009 and May 2019. The data obtained at the time of kidney biopsy were analyzed. After the exclusion of patients without light microscopy and immunofluorescence microscopy findings, a total of 3875 patients were included in the study. RESULTS: The mean age was 41.5 ± 14.9 years. 1690 patients were female (43.6%) and 2185 (56.3%) were male. Nephrotic syndrome was the most common biopsy indication (51.7%). This was followed by asymptomatic urinary abnormalities (18.3%) and nephritic syndrome (17.8%). The most common PGD was IgA nephropathy (25.7%) followed by membranous nephropathy (25.6%) and focal segmental glomerulosclerosis (21.9%). The mean total number of glomeruli per biopsy was 17 ± 10. The mean baseline systolic blood pressure was 130 ± 20 mmHg and diastolic blood pressure was 81 ± 12 mmHg. The median proteinuria, serum creatinine, estimated GFR, and mean albumin values were 3300 (IQR: 1467-6307) mg/day, 1.0 (IQR: 0.7-1.6) mg/dL, 82.9 (IQR: 47.0-113.0) mL/min and 3.2 ± 0.9 g/dL, respectively. CONCLUSIONS: The distribution of PGDs in Turkey has become similar to that in other European countries. IgA nephropathy diagnosed via renal biopsy has become more prevalent compared to membranous nephropathy.

Clinical significance of mesangial IgM deposition in patients with IgA nephropathy.

BACKGROUND: Glomerular immunoglobulin G deposition in patients with immunoglobulin A nephropathy (IgAN) has been shown to be associated with adverse renal outcomes. Clinical significance of mesangial immunoglobulin M (IgM) deposition in these patients remains to be proven. METHODS: One hundred patients who had a diagnosis of IgAN between 2001 and 2017 were enrolled. Patients were divided into two groups based on mesangial IgM deposition status. Groups were compared for demographic, clinical, and pathologic variables at baseline and in follow-up. Cox regression analysis was performed to evaluate the effect of mesangial IgM positivity on renal survival. RESULTS: IgM-positive group included 51% of participants. Baseline demographic and clinical parameters were not significantly different between groups. Mesangial IgM deposition was significantly associated with a higher segmental sclerosis score (p = 0.008). At last visit, median serum creatinine was higher (p = 0.021) and eGFR was lower (p = 0.006) in IgM-positive group. Nineteen (19%) of all patients reached the combined primary outcome which includes doubling in serum creatinine or evolution to ESRD. Cumulative renal survival was lower (p = 0.001) and resistant disease was more frequent in IgM-positive group (p = 0.026). Renal survival at 15 years was 94.2% and 59.7% in IgM-negative and IgM-positive groups, respectively (p = 0.006). Time-averaged proteinuria (HR 2.9; 95% CI 1.9-4.5; p < 0.001) and mesangial IgM deposition (HR, 13.2; 95% CI 1.9-93.1; p = 0.01) were found to be independent predictors of unfavorable renal outcomes. CONCLUSIONS: In conclusion, we demonstrated that mesangial IgM deposition independently associated with worse renal outcomes in patients with IgA nephropathy.

Predictors and histopathological characteristics of non-diabetic renal disorders in diabetes: a look from the tubulointerstitial point of view.

BACKGROUND: Prevalence and characteristics of non-diabetic renal diseases (NDRD) in patients with type 2 diabetes mellitus is different between populations, and seems to be largely dependent on biopsy policies. AIM: To investigate clinical clues for NDRD in patients with type 2 diabetes mellitus and to analyse renal prognosis of patients based on pathological diagnosis. METHODS: We retrospectively searched medical records of 115 patients with type 2 diabetes who underwent a renal biopsy between 2004 and 2018. Patients were divided into three groups as diabetic nephropathy (DN), NDRD + DN or NDRD based on histopathological examination. RESULTS: Thirty-six (31.3%) patients had DN, 33 (28.7%) had DN + NDRD and 46 (40%) had NDRD. The absence of diabetic retinopathy, recent onset of diabetes, abnormal disease chronology, and blood haemoglobin was associated with the presence of NDRD in univariate analysis. Abnormal disease chronology which was defined as the presence of acute proteinuria and/or acute kidney injury that are unexpected to be related to evolution of diabetic nepropathy (odds ratio 4.65, 95% confidence interval 1.44-15.00; P = 0.010) and absence of diabetic retinopathy (odds ratio 3.44, 95% confidence interval 1.32-8.98; P = 0.012) were independently associated with the presence of NDRD in multivariate analysis. Focal segmental glomerulosclerosis was the most frequent type of NDRD. Diseases that affect tubulointerstitial area were more prevalent in the DN + NDRD group compared to the NDRD group (P = 0.001). Renal survival, which was defined as evolution to end-stage renal disease, was 59.5 ± 14.4 months, 93.7 ± 11.7 months and 87.2 ± 2.6 months for DN, DN + NDRD and NDRD groups, respectively (P = 0.005). CONCLUSIONS: Renal biopsy is essential in certain clinical conditions as diagnosis of NDRD is vital for favourable renal survival. DN may facilitate superimposed tubular injury in the presence of toxic insults.

IgA nephropathy: association of C4d with clinical and histopathological findings and possible role of IgM.

BACKGROUND: In patients with IgA nephropathy (IgAN) lectin and alternative pathways of the complement can be activated. Our aim was to analyze the association of glomerular and extraglomerular C4d staining--the representative of lectin pathway-with demographic, clinical and histopathological findings in primary IgAN patients. DESIGN: Seventy-three patients were enrolled and after re-evaluation 37 of them were included in this study. Biopsies were analyzed for staining with anti-C4d primary monoclonal antibody by immunohistochemistry. Patients were classified as positive and negative groups based on their glomerular C4d deposition. Groups were compared for their baseline clinical and histopathological findings. RESULTS: Sixteen (43.2%) of 37 patients were C4d-positive. Glomerular C4d-staining was associated with more severe proteinuria (2906 mg/day vs. 1091 mg/day; p = 0.002), lower GFR (54.87 mL/min vs. 95 mL/min; p = 0.023), higher blood pressure (p = 0.022), more severe endocapillary hypercellularity (p < 0.001) and more severe tubular atrophy (p < 0.01). Mesangial IgM deposition was found to be associated with glomerular C4d staining and nephrotic range proteinuria. CONCLUSIONS: Glomerular C4d deposition was found to be associated with more unfavorable histopathological and clinical findings at the time of diagnosis. Association of mesangial IgM deposition with the activation of lectin pathway is a novel finding. Mesangial IgM deposition in our patients may reflect the genetic heterology of IgAN between diverse populations. However, since these data are about association, a cause-and-effect about IgM and IgAN cannot be proven solely with these findings.

The relationship between changes in peritoneal membrane solute transfer characteristics and cardiac remodeling in patients with peritoneal dialysis.

INTRODUCTION: We aimed to determine the relationship between the dilatation of the heart chambers and the change in peritoneal membrane solute transfer characteristics (PMTC) in long-term peritoneal dialysis (PD) patients. METHODS: This is a retrospective, single-center study including the follow-up of maintenance PD patients. According to the changes in PMTC from baseline to the last visit, patients were divided into three groups; stable (n = 11), increased (n = 41), and decreased transporters (n = 35). RESULTS: Left atrium (LA) and Right ventricle (RV) dilatation were more prominent in the PMTC-decreased group compared to PMTC-increased and stable groups (p < 0.001 and p = 0.07, respectively). The Cox regression analysis showed that only decreased PMTC was associated with LA dilatation (HR 2.89 [CI 95%1.54, 5.45] p < 0.01) and RV dilatation (HR 3.01 [CI 95%1.40, 6.21] p < 0.01). CONCLUSION: PD can be associated with unfavorable dynamic changes in cardiac structure and functions even at the subclinical level.

The association between geriatric nutritional risk index variability and mortality in peritoneal dialysis patients.

BACKGROUND: The objective of this study is to examine the association between the Geriatric Nutritional Risk Index (GNRI) and overall mortality in this population. METHODS: GNRI values were calculated by using the serum albumin levels and body weight and the GNRI variability reflects the changes in GNRI change slopes in the follow-up. RESULTS: GNRI values showed a decrease from the median baseline GNRI of 106.3 (IQR, 95.0,113.4) to 98.4 (interquartile range [IQR], 91.9108.9) (p < 0.001). The median GNRI variability was 4.7 (IQR, 2.5, 10.3). Both baseline GNRI levels (adjusted odds ratio [OR]: 0.96, 95% confidence interval [CI]: 0.93, 0.99, p = 0.04) and more profoundly GNRI variability (adjusted OR: 1.23, 95% CI: 1.01, 1.44, p = 0.03) were independently associated with mortality. CONCLUSION: The monitorization of the changes in GNRI values as a variability index is an easy tool that might improve the predictive accuracy of mortality in peritoneal dialysis patients.

Long-Term Outcomes of Patients With Amyloidosis Following Kidney Transplant.

OBJECTIVES: Reported graft and patient survival rates in amyloidosis after renal transplant differ considerably between studies. MATERIALS AND METHODS: Group 1 included 24 patients who had end-stage renal disease secondary to amyloidosis. Group 2 (the control group) included 24 consecutive patients who had kidney disease secondary to various causes other than amyloidosis. Comparisons between groups were made for kidney and patient survival rates and other complications following kidney transplant. We also compared survival rates of patients in group 1 versus another control group that included patients with amyloidosis who were treated with hemodialysis (group 3; n = 25). RESULTS: Mean follow-up was 109.5 ± 79.8 months. Biopsy-proven acute rejection and graft failure rates were not significantly different between groups. In group 1 versus group 2, the cumulative 10-year and 20-year patient survival rates were 68.2% versus 86.1% and 36.9% versus 60.3%, respectively (P = .041). Survival was not significantly different in group 1 compared with group 2 and group 3, although patients in group 3 had significantly shorter duration of time to death after the start of renal replacement therapy. CONCLUSIONS: Patient survival may be lower in kidney transplant recipients with amyloidosis compared with patients with end-stage renal disease due to other causes. However, graft failure and acute rejection rates seem to be similar.

Role of p38 MAPK, Akt and NFκB in renoprotective effects of nebivolol on renal ischemia-reperfusion injury in rats.

Renal ischemia-reperfusion (I-R) injury is a complex pathophysiologic condition characterized by oxidative stress, inflammation and apoptosis. We investigated the potential renoprotective effect of nebivolol, a ß1 adrenergic receptor blocker, against renal I-R injury. We focused on the role of nebivolol in activating p38 mitogen-activated protein kinase (MAPK) signaling, Akt (protein kinase B) and nuclear factor-κB (NFκB) transcription factors, which contribute to oxidative stress, inflammation and apoptosis during renal I-R. We divided 20 adult male Wistar albino rats into three experimental groups. Group 1 was a sham control in which only laparotomy was performed. Group 2 was the I-R group in which both kidneys were made ischemic for 45 min, then reperfused for 24 h. Group 3 was the I-R + nebivolol group in which 10 mg/kg nebivolol was administrated by gavage for 7 days before I-R. We measured Inflammation, oxidative stress and active caspase-3 as well as activation of p38 MAPK, Akt (protein kinase B) and NFκB transcription factor. Nebivolol significantly reduced oxidative stress and increased superoxide dismutase levels during renal I-R. We found that nebivolol significantly decreased interstitial inflammation, and TNF-α and interleukin-1ß mRNA expression. Nebivolol significantly reduced active caspase-3 and kidney injury molecule-1 (KIM-1) expressions. Nebivolol also significantly decreased activation of p38 MAPK signaling and NFκB, and induced Akt activation during renal I-R. Our findings suggest that nebivolol may be useful for management of renal I-R injury.

Unusual case of severe late-onset cytomegalovirus-induced hemorrhagic cystitis and ureteritis in a renal transplant patient.

Cytomegalovirus (CMV) infection is common in solid organ transplant recipients and accounts for the majority of graft compromise. Major risk factors include primary exposure to CMV infection at the time of transplantation and the use of antilymphocyte agents such as OKT3 (the monoclonal antibody muromonab-CD3) and antithymocyte globulin. It most often develops during the first 6 months after transplantation. Although current prophylactic strategies and antiviral agents have led to decreased occurrence of CMV disease in early posttransplant period, the incidence of late-onset CMV disease ranges from 2% to 7% even in the patients receiving prophylaxis with oral ganciclovir. The most common presentation of CMV disease in transplant patients is CMV pneumonitis followed by gastrointestinal disease. Hemorrhagic cystitis is a common complication following hematopoietic stem cell transplantation. The condition is usually due to cyclophosphamide-based myeloablative regimens and infectious agents. Even in these settings, CMV-induced cases occur only sporadically. Ureteritis and hemorrhagic cystitis due to CMV infection after kidney transplantation is reported very rarely on a case basis in the literature so far. We report here a case of late-onset CMV-induced hemorrhagic cystitis and ureteritis presenting with painful macroscopic hematuria and ureteral obstruction after 4 years of renal transplantation. The diagnosis is pathologically confirmed by the demonstration of immunohistochemical staining specific for CMV in a resected ureteral section. We draw attention to this very particular presentation of CMV hemorrhagic cystitis with ureteral obstruction in order to emphasize atypical presentation of tissue-invasive CMV disease far beyond the timetable for posttransplant CMV infection.

Causes of Granulomatous Inflammation in Native and Allograft Kidneys: Case Series from A Single Center and A Review of the Literature.

OBJECTIVE: Granulomatous interstitial nephritis is a rare finding, and etiology differs by geography. We aimed to investigate the distribution of causes of granuloma/granulomata in the kidney and renal survival of these patients in a tertiary care hospital in Western Turkey. MATERIAL AND METHOD: Medical records of adults who underwent a kidney biopsy procedure in our institution between January 2000 and June 2019 were reviewed. Pathology reports were searched for biopsies where a granuloma was identified. RESULTS: Nineteen of 1121 (1.7%) kidney biopsies included granuloma, 17 in native kidneys, and 2 in transplants. The majority of indications for native kidney biopsy was a rise in serum creatinine. Etiologies of granuloma included the following: pauci-immune vasculitis (n=11, 64.7%), tuberculosis (n=2, 11.8%), drug-induced (n=2, 11.8%), tubulointerstitial nephritis/uveitis (TINU) syndrome (n=1, 5.9%), and systemic-lupus erythematosus (n=1, 5.9%). Despite treatment, 6 of 11 (54.5%) patients with vasculitis developed end-stage kidney disease (ESKD) during the median follow-up of 16 months. Both of the patients with tuberculosis, and the patient with TINU syndrome developed ESKD months after the kidney biopsy, despite appropriate therapies. The only case with drug-induced granuloma and both cases with allograft kidney granuloma responded well to glucocorticoids, achieving a complete renal recovery. CONCLUSION: The majority of our series had granuloma in the kidney secondary to vasculitis and renal outcomes appear considerably unfavorable despite treatment, probably related to the primary diagnosis. Multicenter studies are needed to better determine the etiology and outcome of each granuloma etiology at different geographic locations.

Prevalence of Gastrointestinal Symptoms and Clinical Outcomes in Hospitalized Coronavirus Disease 2019 Patients: A Single-Center Study from Turkey.

BACKGROUND: In patients with coronavirus disease 2019, the gastrointestinal symptoms have been reported increasingly in addition to the respiratory system symptoms. The studies show that the prevalence of gastrointestinal system symptoms and how the gastrointestinal system contributes to the severity and prognosis of the disease is still not clear. This study aims to find the prevalence of gastrointestinal symptoms and the correlation between the gastrointestinal symptoms and the clinical results in hospitalized patients diagnosed with coronavirus disease 2019. METHODS: This study retrospectively analyzes patients diagnosed with coronavirus disease 2019 and hospitalized in the pandemic unit between March 2020 and August 2020 and compares their demographic and clinical characteristics, laboratory and radiologic findings, coronavirus disease 2019 treatments received, the clinical course of the disease, and the gastrointestinal symptoms. RESULTS: In our study, we included 322 patients diagnosed with coronavirus disease 2019 and hospitalized; 39 patients (12.1%) were admitted to the hospital with at least one gastrointestinal symptom (nausea and vomiting, diarrhea, abdominal pain, and the loss of taste). Nausea and vomiting are the most common gastrointestinal symptoms with a prevalence of 7.1%, followed by diarrhea with 2.8%, the loss of taste with 2.2%, and abdominal pain with 1.5%. The mean age and D-dimer levels of the patients showing gastrointestinal symptoms were lower than those who did not have any gastrointestinal symptoms. We did not find a significant correlation between the presence of the gastrointestinal symptoms and the severity of the disease, treatment received, risk of acute respiratory distress syndrome and septic shock, admission to the intensive care unit, the need for mechanical ventilation, the mortality rate or the length of hospitalization in the medical floor or the intensive care unit. CONCLUSION: In this study, we observed that 12.1% of coronavirus disease 2019 patients apply to the hospital due to gastrointestinal symptoms. Furthermore, the gastrointestinal symptoms do not seem to affect the severity and the course of the disease, it is important to identify coronavirus disease 2019 patients showing unusual symptoms such as the gastrointestinal symptoms at an early stage to protect healthcare professionals from infection risk.

Trends of primary glomerular disease in Turkey: TSN-GOLD registry report.

BACKGROUND: Although several renal biopsy registry reports have been published worldwide, there are no data on primary glomerular disease trends in Turkey. METHODS: Three thousand eight-hundred fifty-eight native kidney biopsy records were assessed in the Turkish Society of Nephrology Primary Glomerulopathy Working Group (TSN-GOLD) Registry. Secondary disease and transplant biopsies were not recorded in the registry. These records were divided into four periods, before 2009, 2009 to 2013, 2013-2017, and 2017-current. RESULTS: A total of 3858 patients (43.6% female, 6.8% elderly) were examined. Nephrotic syndrome was the most common biopsy indication in all periods (58.6%, 53%, 44.1%, 51.6%, respectively). In the whole cohort, IgA nephropathy (IgAN) (25.7%) was the most common PGN with male predominance (62.7%), and IgAN frequency steadily increased through the periods (× 2 = 198, p < 0.001). MGN was the most common nephropathy in the elderly (> 65 years), and there was no trend in this age group. An increasing trend was seen in the frequency of overweight patients (× 2 = 37, p < 0.0001). Although the biopsy rate performed with interventional radiology gradually increased, the mean glomeruli count in the samples did not change over the periods. CONCLUSIONS: In Turkey, IgAN is the most common primary glomerulonephritis, and the frequency of this is increasing.

Demographic and clinical characteristics of patients with autosomal dominant polycystic kidney disease: a multicenter experience.

AIM: Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disease. It accounts for 5-10% of patients with end-stage renal disease (ESRD). The aim of this multicenter study was to investigate the demographic and clinical characteristics of patients with ADPKD. METHODS: 1,139 patients with ADPKD who were followed up at 12 different centers were recruited for this study. The investigated demographic and clinical characteristics were gender, age, smoking history, educational status, the existence of hypertension, hematuria, urinary tract infection, urinary tract stones and renal replacement therapy. Patients were considered as hypertensive if they were taking antihypertensive medications or if they had blood pressure (BP) of 140/90 mm Hg or greater. If the patients were currently on antihypertensive drugs, the classes of these agents were noted. RESULTS: 548 male and 591 female patients were included and the mean age at initial diagnosis was 37.1 ± 16.3 years. 20.3% were current smokers whereas 15% were ex-smokers. The mean systolic and diastolic BPs were 136.1 ± 29.8 and 84.9 ± 17.8 mm Hg, respectively. 63.7% used antihypertensive drugs and 73.1% of those used renin-angiotensin system blockers. 11.8% had ESRD, of which 75.8% were treated with hemodialysis. CONCLUSION: This study showed that hypertension is the most common (72.6%) clinical finding in ADPKD patients in Turkey and renin-angiotensin system blockers are widely used.

Tuberculosis in renal transplant recipients.

BACKGROUND: Renal transplant recipients should be considered at high risk for development of Mycobacterium tuberculosis infection (tuberculosis, TB). TB is relatively more frequent among transplant recipients than general population, depending on its epidemicity in the geographic region. Clinical manifestations in this group of patients may be atypical and deserve aggressive investigations for diagnosis. Tuberculin skin test has several limitations regarding diagnosis in chronic renal failure patients. In this retrospective study, we aimed to explore the prevalence and clinical manifestations of TB in renal transplant patients. MATERIALS AND METHODS: We retrospectively analyzed the data for TB prevalence, clinical presentations, and patient and graft survivals of total 320 pediatric and adult renal transplant recipients in our center between 1992 and 2010. RESULTS: The prevalence of TB was 2.8%. Five patients received kidney from living-donor related and four from cadaveric donors. Cadaveric-donor patients received antithymocyte globulin for induction, and four patients received pulse steroid for acute rejection. The median duration of time between transplantation and TB was 21 (1-150) months, and between induction/pulse therapy and infection was 5 (1-100) months. The immunosuppressive protocols included prednisolone and cyclosporine/rapamycin with or without mycophenolate mofetil/azathioprine. The major symptoms were fever (77%), cough (66%), and abdominal pain (22%). Extrapulmonary TB with intestinal (2/9), pericardial (1/9), lymph node (1/9), and cerebral (1/9) involvements developed in five patients. One patient had both pulmonary and testicular involvements. All patients received quartet of anti-TB therapy for a median duration of 9 months. One patient died at the second month of therapy because of dissemination of TB, and one patient returned to hemodialysis because of chronic allograft nephropathy. CONCLUSION: The prevalence of TB was 2.8% in our renal transplant patients. The quartet of anti-TB treatment including rifampicin resulted in success in a majority of patients.

Results of 4-year analysis of conversion from calcineurin inhibitors to mTOR inhibitors in renal transplant patients: single-center experience.

In this retrospective study, 83 patients were accepted. Mammalian target of rapamycin (mTOR) group consisting of 37 patients were converted from calcineurin inhibitors (CNI), and the control group included 46 patients (initially CNI-receiving patients). As a control-match of each mTOR inhibitor patient, the succeeding patient with transplantation who continued CNI therapy was chosen. All patients received CNI, MMF, and prednisolone as an immunosuppressive therapy initially. In comparison of two groups, there was no significant difference between sex, donor organ source, donor organ ischemia time, or mismatches. However, mean age between groups was significantly different (mTOR group: 48.3 ± 12, CNI group: 38.6 ± 11, p < 0.001). Decision of conversion to mTOR inhibitors in 30 patients was made by biopsy. The reasons for conversion were determined as CNI nephrotoxicity in 15 patients, chronic allograft nephropathy in 15 patients, malignancy in 6 patients, and renal artery stenosis in 1 patient. Basal glomerular filtration rates (GFRs) were markedly lower in mTOR group than in CNI group (38.8 mL/min vs. 72.7 mL/min). At the end of 48-month follow-ups, GFR increased from 38 mL/min to 54 mL/min in mTOR group; however, it decreased to 53 mL/min from 72 mL/min in CNI group. There was no difference left between the two groups in GFR after 4-year follow-up. Hyperlipidemia was higher in mTOR group. Acute rejection rates were similar. Cytomegalovirus (CMV) disease was more prevalent in CNI group. Graft failure developed due to secondary reasons, causing mortality in both groups. We suggest that conversion to mTOR inhibitors maintains and improves graft functions well.

Alpha-lipoic acid alleviates colistin nephrotoxicity in rats.

Colistin methanesulfonate (CMS), a clinical form of colistin, is widely used as a last-line treatment for multidrug-resistant (MDR) gram-negative bacterial infections in critically ill patients presenting a considerably high mortality rate. However, nephrotoxicity is considered to be a critical adverse effect that limits CMS's clinical use. Alpha-lipoic acid (ALA) is a strong antioxidant that is effective in preventing nephrotoxicity in many models. The aim of this study was to investigate ALA's ability to protect against nephrotoxicity induced by colistin in rats. Male Wistar albino rats were randomly divided into four groups. Group 1 was the control group (Control; n = 6), in which isotonic saline was administered to the rats. Group 2 was the ALA group (ALA; n = 6) in which rats received 100 mg/kg ALA. Groups 3 was the CMS (CMS; n = 7) in which 450.000 IU/kg/day of CMS was administered to the rats. Groups 4 was the CMS + ALA group (n = 6), in which rats were injected with 100 mg/kg of ALA 30 min before administration of CMS. All injections were performed intraperitoneally at 1, 4, 7, and 10 days. Urine was collected by using a metabolic cage for 24 h after each administration. The rats were euthanized under ether anesthesia after 24 h of the last administration. Blood and kidney samples then were collected for histological and biochemical analysis. ALA pretreatment could reverse the effects of colistin-induced nephrotoxicity, partly through its suppressing effect on Nox4 and caspase-3, which in turn results in its antioxidant and antiapoptotic effect. Therefore, ALA may be an effective strategy for the management of colistin nephrotoxicity.

Acute kidney injury following colistin treatment in critically-ill patients: may glucocorticoids protect?

Nephrotoxicity following colistin administration is common and factors alleviating nephrotoxicity are yet to be determined. We retrospectively evaluated outcomes of subjects who were treated with colistin (n = 133) and with antibiotics other than colistin (control, n = 133) in intensive care units. Acute kidney injury (AKI) occurred in 69.2% and 29.3% of patients in colistin and control groups, respectively (p < 0.001). In the colistin group, glucocorticoid exposure was more common in subjects who did not develop AKI (p < 0.001). This was not the case in the control group. In the colistin cohort, older age (per 10 years, odds ratio [OR] 1.41, 95% CI 1.05-1.91; p = 0.025), PPI use (OR 3.30, 95% CI 1.18-9.23; p = 0.023) and furosemide treatment (OR 2.66, 95% CI 1.01-6.98; p = 0.047) were independently associated with the development of AKI while glucocorticoid treatment (OR 0.23, 95% CI 0.10-0.53; p = 0.001) was independently associated with reduced risk of AKI. Mortality was observed in 74 patients in the colistin cohort (55.6%). A higher APACHE-II score (OR 1.17, 95% CI 1.08-1.26; p < 0.001) was independently associated with mortality while a higher serum albumin level (per 1 g/dL increase, OR 0.20, 95% CI 0.070-0.60; p = 0.004) was associated with a lower risk of mortality. In conclusion, glucocorticoid exposure is associated with a lower risk of AKI caused by colistin therapy in critically-ill patients. Prospective studies are needed to confirm these findings and determine the optimal type, dose and duration of glucocorticoid therapy.