Evaluation of the Renal and Cardiovascular Effects of Long-Term Tolvaptan Treatment in Autosomal Dominant Polycystic Kidney Disease.

INTRODUCTION: Cardiovascular diseases constitute a significant cause of morbidity and mortality in individuals with autosomal dominant polycystic kidney disease (ADPKD). This study aimed to assess the long-term effects of tolvaptan on the kidneys and heart in rapidly progressing ADPKD. METHODS: Among 354 patients diagnosed with ADPKD, 58 meeting the eligibility criteria for tolvaptan were included in the study. The study comprised two groups with similar demographic and clinical characteristics: 29 patients receiving tolvaptan treatment and 29 in the control group. Several included genetic analysis, magnetic resonance imaging, and echocardiography. Clinical and cardiac changes were recorded in both groups after a 3-year follow-up. RESULTS: Tolvaptan treatment demonstrated a significant reduction in the rate of eGFR decline compared to the control group. Furthermore, it was observed that tolvaptan could prevent the development of cardiac arrhythmias by inhibiting an increase in QTc interval and heart rate. CONCLUSION: These findings suggest that, in addition to slowing kidney progression in ADPKD management, tolvaptan may potentially benefit in preventing cardiac complications.

The effect of footbath applied to patients receiving hemodialysis treatment on comfort, fatigue, and dialysis symptoms: A randomized controlled study.

INTRODUCTION: This study aimed to evaluate the effect of warm water footbaths on comfort, fatigue, and dialysis symptoms in patients undergoing hemodialysis. METHODS: Data were collected from a total of 58 patients, 31 in the intervention group and 27 in the placebo group. The data in the study are collected using the intervention and control group informed volunteer Form, Patient Demonstration Form, foot Bath Application Monitoring Chart, fatigue VAS Scale Form, Dialysis Symptom Index, and Hemodialysis Comfort Scale (HCS). RESULTS: In the second follow-up in the intervention group, HCS was determined to significantly increase all sub-size and total score averages by the first trace (p < 0.05). VAS fatigue point averages were significantly lower (p < 0.05) in the intervention group. CONCLUSION: It was determined that the footbath applied to patients who received hemodialysis treatment increased comfort and reduced fatigue and dialysis symptoms.

An unusual form of kidney injury without glomerulonephritis in microscopic polyangiitis: a case report.

BACKGROUND: Microscopic polyangiitis (MPA), a kind of antineutrophil cytoplasmic autoantibody associated vasculitis (AAV), predominantly affects small-sized vessels. MPA is a significant cause of the pulmonary-renal syndrome. Pauci-immune necrotizing and crescentic glomerulonephritis is the typical renal histological feature of AAV. Tubulointerstitial lesions may occur and mostly form with inflammatory cell infiltration in the interstitium. However, a few cases reported only tubulointerstitial involvement without glomerular lesions in patients with MPA. CASE PRESENTATION: We present an MPA case, a 70-year-old male patient diagnosed with acute kidney injury accompanying the dialysis requirement. Only acute tubulointerstitial nephritis was revealed in kidney biopsy without evidence of glomerular injury. Also, interstitial pulmonary fibrosis was determined on computerized tomography, and myeloperoxidase antineutrophil cytoplasmic autoantibody was positive. Consequently, we have considered the main diagnosis as MPA. We did not prefer a standard tubulointerstitial nephritis treatment regimen due to the presence of life-threatening systemic vasculitis. Treatment was established like crescentic glomerulonephritis. Induction therapy consisted of pulse steroid, cyclophosphamide, and plasmapheresis. Unfortunately, severe SARS-CoV-2 infection caused death during induction therapy in this case. CONCLUSIONS: The lack of glomerular injury and solely interstitial inflammation is atypical regarding AAV involvement in the kidney. This diversity might be initially considered as only a simple histological elaboration. However, it is a significant entity for guiding the treatment of AAV.

Demographic, clinical and laboratory characteristics of adult-onset minimal change disease in Turkey: Turkish Society of Nephrology-Glomerular Diseases (TSN-GOLD) Working Group.

PURPOSE: In our study, diagnostic and demographic characteristics of patients diagnosed with minimal change disease (MCD) by biopsy, clinical and laboratory findings in our country were investigated. METHODS: Data were obtained from the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD) Working Group database. Demographic characteristics, indications for biopsy, diagnosis of the glomerular diseases, comorbidities, laboratory and biopsy findings of all patients were recorded. The data presented are cross-sectional and includes application data for the biopsy period. RESULTS: Of 3875 patients, 233 patients with MCD (median age 35.0 years) were included in the study, which constitutes 6.0% of the total glomerulonephritis database. Renal biopsy was performed in 196 (84.1%) patients due to nephrotic syndrome. Median serum creatinine was 0.7 (0.6-1.0) mg/dl, mean eGFR was 104 ± 33 ml/min/1.73 m2 and median proteinuria 6000 mg/day. The number of patients under the age of 40 years was 139 (59.7%) (Group A), and the number of patients aged 40 years and over was 94 (40.3%) (Group B). Compared to Group A, global sclerotic glomeruli (24 vs. 43, p < 0.001) interstitial inflammation (15 vs. 34, p < 0.001), interstitial fibrosis (20 vs. 31, p = 0.001, vascular changes (10 vs. 25, p < 0.001) and tubular atrophy (18 vs. 30, p < 0.001) were found to be significantly higher in Group B. There was no difference in immunofluorescent staining properties between the two groups. CONCLUSION: Our data are generally compatible with the literature. Chronic histopathological changes were more common in patients aged 40 years and older than younger patients. Studies investigating the effects of these different features on renal survival are needed.

C allele in transforming growth factor-ß1 rs1800471 gene polymorphisms might indicate a protective feature in encapsulating peritoneal sclerosis development.

INTRODUCTION: Peritoneal fibrosis may progress in peritoneal dialysis (PD) patients to a fatal clinical condition called encapsulating peritoneal sclerosis (EPS). Transforming growth factor (TGF)-ß plays a pivotal role in the pathogenesis of peritoneal fibrosis. We aimed to investigate the association among polymorphisms in the gene encoding TGF-ß1, which were -509C/T (rs1800469), +869T/C (rs1982073), and +915G/C (rs1800471) in EPS patients. METHODS: A total of 16 PD patients who were clinically and radiologically diagnosed with EPS were enrolled and 22 age- and gender-matched PD patients were selected as the non-EPS group. RESULTS: G allele frequency at the rs1800471 gene polymorphism was significantly higher in the EPS group than non-EPS group (p = 0.005). Interestingly, the non-EPS group patients had CC or CG polymorphisms. CONCLUSION: C allele in TGF-ß1 rs1800471 gene polymorphisms might indicate a protective feature in EPS development. Knowing the presence of polymorphism may be effective in selecting renal replacement therapy in patients.

Evaluation of the causes affecting the development of pruritus in patients with peritoneal dialysis.

BACKGROUND: Several factors play a role in the pathogenesis of pruritus in uremic patients. The pathophysiology is complex and many factors have been identified in these patients. The aim of this study was to investigate the presence, severity, and possible causes of pruritus in patients with peritoneal dialysis (PD) . METHODS: Eighty patients, who received continuous ambulatory peritoneal dialysis (CAPD) treatment, were included in this study. Biochemical measurements, parathormone, C-reactive protein (CRP), and vitamin B12 levels of all the patients were recorded. Furthermore, substance P (SP) levels were measured by ELISA methods. Patients were examined by a dermatologist and pruritus degrees were queried using the visual analog score (VAS) with skin dryness. RESULTS: In generalized linear model analysis, total urea clearance and SP independently predicted VAS scores. SP was significantly predictive in ROC analysis in identifying the VAS score in patients with peritoneal dialysis. The sensitivity and specificity of SP were 80% and 67% (cut-off > 364), respectively, with an area under the ROC curve of 0.757 (95% CI 0.650-0.865, p < 0.001). SP also was significantly predictive in ROC analysis in identifying xerosis in PD patients. CONCLUSION: Pruritus was proportional to the amount of substance P and total urea clearance was another reason affecting pruritus in peritoneal dialysis patients.

Effect of Serum Albumin Changes on Mortality in Patients with Peritoneal Dialysis: A Joint Modeling Approach and Personalized Dynamic Risk Predictions.

Peritoneal dialysis (PD) is a frequently used and growing therapy for end-stage renal diseases (ESRD). Survival analysis of PD patients is an ongoing research topic in the field of nephrology. Several biochemical parameters (e.g., serum albumin, creatinine, and blood urea nitrogen) are measured repeatedly in the follow-up period; however, baseline or averaged values are primarily associated with mortality. Although this strategy is not incorrect, it leads to information loss, resulting in erroneous conclusions and biased estimates. This retrospective study used the trajectory of common renal function indexes in PD patients and mainly investigated the association between serum albumin change and mortality. Furthermore, we considered patient-specific variability in serum albumin change and obtained personalized dynamic risk predictions for selected patients at different follow-up thresholds to investigate the effect of serum albumin trajectories on patient-specific mortality. We included 417 patients from the Erciyes University Nephrology Department whose data were retrospectively collected using medical records. A joint modeling approach for longitudinal and survival data was used to investigate the relationship between serum albumin trajectory and mortality of PD patients. Results showed that averaged serum albumin levels were not associated with mortality. However, serum albumin change was significantly and inversely associated with mortality (HR: 2.43, 95% CI: 1.48 to 4.16). Risk of death was positively associated with peritonitis rate, hemodialysis history, and the total number of comorbid and renal diseases with hazard ratios 1.74, 3.21, and 1.41. There was also significant variability between patients. The personalized risk predictions showed that overall survival estimates were not representative for all patients. Using the patient-specific trajectories provided better survival predictions within the follow-up period as more data become available in serum albumin levels. In conclusion, using the trajectory of risk predictors via an appropriate statistical method provided better predictive accuracy and prevented biased findings. We also showed that personalized risk predictions were much informative than overall estimations in the presence of significant patient variability. Furthermore, personalized estimations may play an essential role in monitoring and managing patients during the follow-up period.

Characteristics of primary glomerular diseases patients with hematuria in Turkey: the data from TSN-GOLD Working Group.

PURPOSE: Hematuria is one of the most common laboratory findings in nephrology practice. To date, there is no enough data regarding the clinical and histopathologic characteristics of primary glomerular disease (PGD) patients with hematuria in our country. METHODS: Data were obtained from national multicenter (47 centers) data entered into the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD) database between May 2009 and June 2019. The data of all PGD patients over the age of 16 years who were diagnosed with renal biopsy and had hematuria data were included in the study. Demographic characteristics, laboratory and biopsy findings were also recorded. RESULTS: Data of 3394 PGD patients were included in the study. While 1699 (50.1%) patients had hematuria, 1695 (49.9%) patients did not have hematuria. Patients with hematuria had statistically higher systolic blood pressure, serum blood urea nitrogen, creatinine, albumin, levels and urine pyuria. However, these patients had statistically lower age, body mass index, presence of hypertension and diabetes, eGFR, 24-h proteinuria, serum total, HDL and LDL cholesterol, and C3 levels when compared with patients without hematuria. Hematuria was present 609 of 1733 patients (35.8%) among the patients presenting with nephrotic syndrome, while it was presented in 1090 of 1661 (64.2%) patients in non-nephrotics (p < 0.001). CONCLUSION: This is the first multicenter national report regarding the demographic and histopathologic data of PGD patients with or without hematuria. Hematuria, a feature of nephritic syndrome, was found at a higher than expected in the PGDs presenting with nephrotic syndrome in our national database.

Soluble vascular endothelial growth factor receptor-1 as a novel marker of arteriovenous fistula stenosis in hemodialysis patients.

INTRODUCTION: Arteriovenous fistula (AVF) stenosis is one of the most important clinical problems in hemodialysis patients. The histopathological findings of neointimal hyperplasia and impaired angiogenesis have been well established in stenotic AVFs. Soluble vascular endothelial growth factor receptor-1 (sVEGFR-1) has been implicated in pathological angiogenesis. Thus, we aimed to investigate the association between sVEGFR-1 and AVF stenosis in hemodialysis patients. METHODS: This prospective cohort study included 70 patients with end-stage renal disease. Forty-five patients were included in the final analysis, and the median follow-up period was 36 months. Venous stenosis was detected by physical examination and documented by fistulography. Blood samples were analyzed a day before the fistula operation, and serum levels of sVEGFR-1 were measured. FINDINGS: The median sVEGFR-1 level was higher in the stenosis group than in the nonstenosis group (17 pg/mL [89.5%] vs. 5 pg/mL [19.2%], respectively; P < 0.001]. According to body mass index (BMI) categories, obese patients (BMI > 30 kg/m2 ) had the shortest stenosis-free survival (20 months [9.35-30.65]). Multivariate Cox analysis showed that sVEGFR-1, serum creatinine, and parathyroid hormone levels were associated with AVF stenosis risk. Kaplan-Meier survival curves showed that patients with less than the median value of sVEGFR-1 (<6093.07 pg/mL) had longer cumulative stenosis-free survival than patients with sVEGFR-1 levels above the median value (P < 0.001). DISCUSSION: Increased levels of sVEGFR-1 and obesity were found to be associated with AVF stenosis in hemodialysis patients.

A rare complication following internal jugular vein catheterization to malposition: acute Budd Chiari syndrome.

BACKGROUND: Tunneled catheters can be used as an alternative vascular access in patients with limited health expectancy,vascular access problems and several comorbidities. We aimed to present a patient with venous stenosis related- reversible acute Budd-Chiari syndrome after catheter malposition. CASE PRESENTATION: After changing of tunneled catheter insertion, 36-year old man was admitted to our hospital with sudden onset of nausea, fever, chills and worsening general condition In computed tomography (CT) imaging, a hypodense thrombus was observed in which the distal end of the catheter is at the level of drainage of the hepatic veins in the inferior vena cava and that blocked hepatic vein drainage around the catheter. The catheter was removed and a new catheter was inserted in the same session. Because patient's general condition was good and without fever, he was discharged with advices on the 9th day of hospitalization. CONCLUSION: Although catheter malposition and thrombosis are not a common complication, clinicians should be alert of these complications.

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.

The effect of sodium exchange and dialytic biochemical parameters on blood pressure, arterial stiffness, and endothelial functions in patients with peritoneal dialysis.

OBJECTIVE: This study aimed to investigate the relationship between fluid and sodium excretion and blood pressure, echocardiographic parameters, and arterial stiffness in peritoneal dialysis (PD) patients and to evaluate the effect of sodium excretion on patients' survival. METHOD: This study was conducted as a single-centered, prospective study in the Department of Nephrology in Erciyes University. The patients included in the study were followed up for 3 years. Seventy PD patients were included in the study. We recorded demographic characteristics, biochemical parameters, urine and peritoneal ultrafiltration volumes, peritoneal equalization tests, ambulatory blood pressure measurements, and echocardiographic measurements. We measured the amount of total sodium excretion of the patients and arterial stiffness using pulse wave velocity (PWV). Patients were divided into two groups based on the amount of total sodium excretion: low group and high group. We compared these groups in terms of cardiac and biochemical parameters. RESULTS: When demographic data and biochemical values were compared, there was no significant difference between the two groups. NT-proBNP level, systolic blood pressure, and mean arterial pressure were significantly higher in the low group (p: 0.02, p: 0.031, p: 0.05, respectively). Net ultrafiltration was significantly higher in the high group (p: 0.03), was also found to be high in patients with high sodium excretion (p: 0.001). Negative correlations were found between sodium excretion and net ultrafiltration, NT-Pro BNP, and PWV. At the end of the 3-year follow-up, the survival rate was shorter and the mortality rate was higher in the low group (p: 0.042). DISCUSSION AND CONCLUSION: Fluid status in PD patients can affect arterial stiffness both directly and through hypertension. Correction of hypervolemia has the potential to not only prevent hypertension and left ventricular hypertrophy, but also to improve arterial stiffness, a well-known cardiovascular risk factor. The mortality rate was higher in PD patients with low total sodium excretion. Therefore, these patients should be followed more closely to ensure volume control.

Hypoxia-inducible factors in arteriovenous fistula maturation: A prospective cohort study.

BACKGROUND: Neointimal hyperplasia is the main cause of arteriovenous fistula (AVF) failure. Hypoxia-inducible factors (HIFs) factors are associated with neointimal hyperplasia. Thus, we investigated the association between HIF-2 alpha (HIF-2α) and AVF maturation in end-stage kidney disease (ESKD) patients. METHODS: This prospective cohort study was conducted in 21 voluntary healthy subjects and 50 patients with ESKD who were eligible for AVF creation. Inclusion criteria were being ESKD patients without a history of AVF surgery and dialysis. Eight patients excluded from the study due to having unavailable veins six patients were excluded due to acute thrombosis after surgery. One patient lost to follow-up. A total of 35 patients were included in final analysis. The blood samples were collected a day before the AVF surgery for biochemical parameters and HIF-2α measurement. HIF-2α levels were measured by the ELISA method. RESULTS: Compared with healthy subjects, ESKD patients had a significantly higher level of HIF-2α. [1.3 (1.0-1.9) vs 2.2 (1.6-3.0)] (P = .002). Patients were divided into two groups after the evaluation of AVF maturation, as the mature group (n = 19) and the failure group (n = 16). Serum HIF-2α level was 1.7 (1.1-1.8) in the mature group; however, it was 3.1 (2.8-3.3 in failure group (P < .001). Multiple logistic regression analyses showed that HIF-2α independently predicted AVF maturation. The ROC curve analysis showed that HIF-2α > 2.65 predicted AVF maturation failure with the 87% sensitivity and 94% specificity [AUC:0.947, 95% CI (0.815-0.994), P < .001]. CONCLUSIONS: HIF-2-α levels were higher in ESKD patients than healthy subjects. HIF-2-α could be a marker of AVF maturation failure.

Association of OSR-1 With Vascular Dysfunction and Hypertension in Polycystic Kidney Disease.

Autosomal-dominant polycystic kidney disease (ADPKD) is associated with oxidative stress and hypertension development before renal function decline and cardiovascular disease development. Oxidative stress-responsive kinase-1 (OSR-1) participates in the signaling regulating Na+ transport during oxidative stress and also plays a role in the regulation of cell volume and blood pressure. Therefore, we aimed to investigate the potential role of OSR-1 in ADPKD patients. Eighty ADPKD patients, 80 healthy controls, and 80 non-ADPKD patients with hypertension were enrolled in this cross-sectional study. Twenty-four-hour ambulatory blood pressure monitoring was conducted in all participants. Blood samples were taken after 12-h fasting for the measurement of biochemical parameters and OSR-1 gene expression. Vascular dysfunction was assessed using ischemia-induced forearm flow-mediated vasodilation (FMD). Briefly, of the 80 ADPKD patients, 41(51%) were male, and 53(66%) of them were hypertensive. The mean age of the 80 controls was 35.3 ± 12.6 years, and 37(46%) of them were male. The mean age of the 80 non-ADPKD patients with hypertension was 44.6 ± 11.9 years, and 38(47.5) of them were male. There were significant differences in serum OSR-1 gene expression between the ADPKD patients and the control subjects. Serum OSR-1 gene expression was also significantly increased in hypertensive ADPKD patients in comparison with both normotensive ADPKD counterparts and non-ADPKD hypertensive subjects. Serum OSR-1 gene expression was increased in patients with ADPKD than healthy subjects. Low estimated glomerular filtration rate (eGFR), OSR-1 gene expression, total kidney volume (TKV), and high-density lipoprotein (HDL) were also independently associated with hypertension in ADPKD patients.

Successful treatment of tubulointerstitial nephritis in immunoglobulin G4-related disease with rituximab: A case report.

BACKGROUND: Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated condition that consisted of disorders that share particular clinical, serologic and pathologic properties. The common presentation of disease includes tumor-like swelling of involved organs and the histopathological findings are a lymphoplasmacytic infiltrate enriched with IgG4-positive plasma cells, and a variable degree of fibrosis that has a characteristic "storiform" pattern in biopsy specimens of tumor-like masses. Major presentations of this disease, which often affects more than one organ, include autoimmune pancreatitis, salivary gland disease (sialadenitis), orbital disease and retroperitoneal fibrosis. The steroid treatment is essential for the treatment of the disease however, other immunosuppressive drugs including cyclophosphamide or rituximab could be an option in resistant cases. CASE SUMMARY: Herein, we reported a 34-year-old woman whom previously had diagnosed with asthma, rheumatoid arthritis and Sjögren's syndrome (SS) referred our nephrology department due to acute kidney failure development at the last rheumatology visit. After kidney biopsy she has been diagnosed with IgG4-RD and tubuluointerstitial nephritis. She had been accepted resistant to steroid, mycophenolate mofetil, methotrexate and azathioprine therapies due to receiving in last two years. She refused to receive cyclophosphamide due to potential gonadotoxicity of the drug. Thus, rituximab therapy was considered. She received 1000 mg infusion, 15 d apart and 6 mo later it has been administered same protocol. After one year from the last rituximab dose serum creatinine decreased from 4.4 mg/dL to 1.6 mg/dL, erythrocyte sedimentation rate decreased from 109 mm/h to 13 mm/h [reference range (RR) 0-20], and C-reactive protein decreased from 55.6 mg/L to 5 mg/L (RR 0-6). All pathologic lymph nodes and masses were also disappeared. CONCLUSION: Patients with IgG4-RD usually misdiagnosed with rheumatologic diseases including systemic lupus erythematous or SS and also they were screened for the presence of malignancy. Rituximab could be an important treatment option in cases with steroid resistant tubulointerstitial nephritis in IgG4-RD.

Systemic Succinate, Hypoxia-Inducible Factor-1 Alpha, and IL-1ß Gene Expression in Autosomal Dominant Polycystic Kidney Disease with and without Hypertension.

BACKGROUND AND OBJECTIVES: Cyst pressure induces renin-angiotensin-aldosterone system activation and kidney hypoxia in autosomal dominant polycystic kidney disease (ADPKD). Lipopolysaccharide-induced Toll-like receptor activation causes metabolic disturbances that are triggered by increased succinate levels and hypoxia inducible factors, which results in inflammation via IL-1ß activation. Since we aimed to investigate the role of both inflammation and hypoxia in the clinical course of ADPKD, via succinate levels from sera samples, HIF-1α gene expression from whole blood and urine samples and IL-1ßgene expression from whole blood were measured. METHODS: One hundred ADPKD patients and 100 matched healthy controls were enrolled to this cross-sectional study. Twenty-four-hour ambulatory blood pressure monitoring was conducted in all participants. Blood, serum, and urine samples were taken after 12-h fasting for the measurement of biochemical parameters and succinate levels. Whole blood and urine samples were used for HIF-1α and IL-1ß geneexpression by using quantitative real-time PCR. RESULTS: There were significant differences in whole blood HIF-1α, IL-1ß geneexpression, and serumsuccinate levels between the ADPKD patients and the control subjects. Whole blood HIF-1αgene expression, IL-1ß geneexpression, and serumsuccinate levels were also significantly different in ADPKD patients with hypertension in comparison with normotensive ones (p < 0.05). Serum succinate levels and blood IL-1ß geneexpression were increased in ADPKD patients with high levels of HIF-1α geneexpression (p = 0.018 and p = 0.029, respectively). CONCLUSIONS: Increased age,low eGFR, and HIF-1α and IL-1ß geneexpressions were also independently associated with hypertension in ADPKD patients. Inflammation and hypoxia are both relevant factors that might be associated with hypertension in ADPKD.

Multiple urinary tract infections are associated with genotype and phenotype in adult polycystic kidney disease.

BACKGROUND: Urinary tract infections (UTI) are one of the important clinical presentations in patients with autosomal dominant polycystic kidney disease (ADPKD). The association between UTI among genotypic and phonotypic properties of ADPKD patients is still obscure. Thus, we investigated the relationship between UTI and polycystin gene mutation with total kidney volume. METHODS: Forty patients with ADPKD patients with a history of more than two UTI and age-gender-matched 40 ADPKD patients without UTI history enrolled in the study. Ambulatory blood pressure monitoring was performed in all participants. Magnetic resonance imaging (MRI) was performed with a 1.5-T system, and total kidney volumes were calculated using mid-slice technique. To determine PKD1 and PKD2 genotype, we performed molecular and genetic tests involving the following steps: DNA isolation, next-generation sequencing (NGS) and data analysis. RESULTS: ADPKD patients with UTI had lower eGFR values than those without UTI [64.9 (32.2-100.8) vs 89.5 (59.0-110.0) (p = 0.041)]. In addition, patients with UTI had significantly increased height-adjusted total kidney volume than patients without UTI [950 (290-1350) vs 345 (243-780.0) (p = 0.005)]. Multiple logistic regression analysis showed that the PKD1-truncating mutation and hTKV independently predicted UTI. The sensitivity and specificity of hTKV were 65% and 77% (cutoff > 727 cm3) with an area of under the ROC curve of 0.70 (95% CI 0.56-0.85, p = 005). CONCLUSIONS: ADPKD patients with larger kidneys and PKD1 mutation are susceptible to increased risk of multiple UTI. Additionally, renal function decreased in ADPKD patients with multiple UTI history.

Brown tumor of the thoracic spine presenting with paraplegia in a patient with peritoneal dialysis.

Secondary and tertiary hyperparathyroidism is an important problem of chronic kidney disease. Brown tumor is a benign, unusual, reactive lesion as a result of disturbed bone remodeling, from long-standing increase in parathyroid hormone level. Brown tumors may cause morbidity due to pressure symptoms on neural structures and spontaneous bone fractures. Herein, we presented a peritoneal dialysis patient with tertiary hyperparathyroidism under calcand calcitriol treatment for 4 years due to refusing of the parathyroidectomy operation. She admitted to hospital for sudden onset back pain with difficulty in gait and walking, and imaging studies showed an expansile mass lesion in the thoracic spine. She was operated for mass and diagnosed with brown tumor. After operation, she lost the ability of walking than become paraplegic and she underwent rehabilitation program. Preventive measures including calcitriol and cinacalcet may cause a modest decrease in parathyroid hormone levels but it should be remembered for the development of bone complications such as brown tumor formation in patients with moderate elevated PTH levels, especially those with tertiary hyperparathyroidism. Parathyroidectomy should be performed without delay in these cases.

Dysmetabolic markers predict outcomes in autosomal dominant polycystic kidney disease.

BACKGROUND: Overweight and obesity were recently associated with a poor prognosis in patients with autosomal dominant polycystic kidney disease (ADPKD). Whether the metabolic consequences of obesity as defined by the metabolic syndrome (MS) are also linked with disease progression remains untested. METHODS: Eligible ADPKD patients with different stages of CKD (n = 105) and 105 non-diabetic controls matched for CKD stage were enrolled in the study. Groups were evaluated at baseline for presence of MS, blood markers of metabolism, homeostasis model assessment of insulin resistance (HOMA-IR) score, and biochemical markers of inflammation (hs-CRP, IL-1ß, IL-6, TNF-α and PON-1). MS was defined according to the National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III). Patients were followed for 12 months and progression defined as a decrease in baseline eGFR > 10%. RESULTS: MS and hypertension were more prevalent amongst ADPKD patients than in the control group. Meanwhile, markers of inflammation such as hs-CRP (3.63 [3.45-5.17] vs. 4.2 [3.45-8.99] mg/dL; p = 0.014), IL-6 (21.65 [14.1-27.49] vs. 24.9 [16.23-39.4] pg/mL; p = 0.004) and IL-1ß (21.33 [15.8-26.4] vs. 26.78 [18.22-35] pg/mL; p < 0.001) levels were all more elevated in ADPKD patients than in non-diabetic CKD subjects. In multivariate analysis having a truncating PKD1 mutation predicted (OR 1.25 [1.09-1.43]; p = 0.002) fulfilling the MS criteria. Finally, ADPKD patients fulfilling MS criteria had a significantly more rapid progression during 12 months of follow-up than did those that did not (OR 3.28 [1.09-9.87]; p = 0.035). CONCLUSIONS: Our data supports the notion that dysmetabolisms part of the ADPKD phenotype and associated with a poor outcome, especially in patients with a truncating PKD1 mutation.

Effects of thymoquinone in prevention of experimental contrast-induced nephropathy in rats.

OBJECTIVES: This study aimed to show the effects of thymoquinone, which is known for its antioxidant, anti-inflammatory, and renal protective effects in contrast-induced nephropathy. MATERIALS AND METHODS: This is an experimental study in rats. 7 groups were included within the scope of our study: sham-vehicle (n=3), premedication-control (n=6), model (n=6), isolated thymoquinone (n=3+3), low-dose thymoquinone (n=6), and high-dose thymoquinone (n=7). In addition to 48 hr of water deprivation, we pre-medicated the rats with intra-peritoneal indomethacin and L-NAME administration. After premedication, 12.5 ml/kg dose of a high osmolar contrast agent-diatrizoat (Urografin %76) was administrated. Thymoquinone was administrated in two different doses of 1 mg/kg and 1.75 mg/kg for four days intraperitoneally. Renal functions, histopathological differences, oxidative stress parameters, and inflammatory indicators of rats were evaluated at the end of the study. RESULTS: Significant decreases were observed in levels of serum creatinine and serum BUN with low-dose thymoquinone (1 mg/kg) administration. In light microscopy, significantly less histopathological damage was observed in the low-dose thymoquinone group compared to the contrast agent group. While high-dose thymoquinone is accepted as ineffective biochemically, toxic evidence was identified histopathologically. There were no significant differences between M and TA groups for serum MDA and SOD levels, which were compared to evaluate oxidative stress (P:0.99, P:0.98; respectively). TNF-α, iNOS, and NF-кB gene expressions were not significantly different between all groups (P:0.748, P:0.531, P:0.910; respectively). CONCLUSION: This experimental study has demonstrated for the first time the protective effect of the TQ substance for CIN in 1 mg/kg dose, in the accompaniment of biochemical and histopathological data in rats.