Glomerulopathies with Fibrillary Deposits.

The glomerulopathies associated with the deposition of extracellular fibrils in the glomeruli are subdivided into Congo red positive (amyloidosis) and Congo red negative (non-amyloidotic glomerulopathies) based on Congo red staining. The non-amyloidotic glomerulopathies are divided into immunoglobulin-derived and non-immunoglobulin-derived glomerulopathies. The immunoglobulin-derived glomerulopathies: fibrillary glomerulopathy (FGn) and immunotactoid glomerulopathy (ITG) are rare glomerulopathies. The diagnosis of fibrillary-immunotactoid glomerulopathy depends on electron microscopy, which shows the presence of microfibrils in the glomeruli. The microfibrils in FGn are randomly arranged with diameters less than 30 nm. The microfibrils in ITG are larger than 30 nm with a visible lumen (microtubules), focally arranged in parallel bundles. Patients with fibrillary-immunotactoid glomerulopathy present with proteinuria (usually in the nephrotic range), microscopic hematuria, arterial hypertension, and chronic kidney disease that progresses to kidney failure over months to years. Currently, there are no guidelines for the treatment of fibrillary-immunotactoid glomerulopathy, although immunotactoid glomerulopathy could be associated with underlying hematologic disorders with the need for clone-directed therapy.

Uric acid and left ventricular hypertrophy: another relationship in hemodialysis patients.

BACKGROUND: The impact of serum uric acid (UA) on morbidity and mortality in hemodialysis (HD) patients is quite controversial in relation to the general population. The aim of this study was to evaluate the association of serum UA with both mortality and left ventricular hypertrophy (LVH) in HD patients. METHODS: This longitudinal study enrolled 225 prevalent HD patients who were classified into three groups according to their follow-up-averaged UA (FA-UA) levels: low FA-UA (FA-UA <400 µmol/L), intermediate/reference FA-UA (FA-UA between 400 and 450 µmol/L) and high FA-UA (FA-UA >450 µmol/L). Echocardiography was performed on a nondialysis day and the presence of LVH was defined based on a left ventricular mass index (LVMI) >131 and >100 g/m2 for men and women, respectively. The patients were followed during a 60-month period. RESULTS: The mean FA-UA level was 425 ± 59 µmol/L (range 294-620). There was a consistent association of higher FA-UA with better nutritional status (higher body mass index, normalized protein catabolic rate, creatinine, albumin and phosphorus), higher hemoglobin, but lower C-reactive protein and LVMI. During the 5-year follow-up, 81 patients died (36%) and the main causes of death were cardiovascular (CV) related (70%). When compared with the reference group, the hazard ratio for all-cause mortality was 1.75 [95% confidence interval (CI) 1.02-2.98; P = 0.041] in the low FA-UA group, but there was no significant association with the high FA-UA group. In contrast, FA-UA did not show an association with CV mortality neither with the lower nor with the high FA-UA group. The unadjusted odds ratio (OR) of LVH risk in the low FA-UA compared with the reference FA-UA group was 3.11 (95% CI 1.38-7.05; P = 0.006), and after adjustment for age, gender, diabetes and CV disease, ORs for LVH persisted significantly only in the low FA-UA group [OR 2.82 (95% CI 1.16-6.88,); P = 0.002]. CONCLUSIONS: Low serum UA is a mortality risk factor and is associated with LVH in HD patients. These results are in contrast with the association of UA in the general population and should be the subject of further research.

Peritoneal Dialysis-Related Peritonitis: Rate, Clinical Outcomes and Patient Survival.

Peritoneal dialysis-related peritonitis remains the major complication and primary challenge to the long-term success of peritoneal dialysis (PD). The study aimed to analyze the peritonitis rate, the cause, the outcomes, and the association of peritonitis with the survival of patients on peritoneal dialysis. Patient data were collected retrospectively from medical charts. A total of 96 patients received peritoneal dialysis in the PD center from 1 January 1999 to 31 December 2018. Episodes of peritonitis (n=159) were registered in 54 (56.3%) patients. The study population was divided into two groups, a group of patients (n=54) who experienced peritonitis and a group of patients free of peritonitis (n=42). The peritonitis rate was 0.47 episodes per patient year. The majority of causative microorganisms were gram-positive bacteria (53.5%). Outcomes of the episodes of peritonitis were resolved infection in 84.9% of episodes, catheter removal in 11.3% of episodes, and death in 3.8% of the episodes of peritonitis. A Kaplan-Meier analysis and log-rank test revealed that the group with peritonitis tended to survive significantly longer than the peritonitis-free group. A 67% reduction rate in the risk of patient mortality was observed for the peritonitis group compared with the peritonitis-free group (hazard ratio: 0.33, 95% CI 0.19-0.57, P=0.000). The prevention and management of PD-related infections, resulted in their worldwide reduction, supporting the use of PD as a first-line dialysis modality.

Complications and Risks of Percutaneous Renal Biopsy.

BACKGROUND: Renal biopsy performed in native and transplant kidneys is generally considered a safe procedure. AIM: In this study, we evaluated renal biopsy complications and risk factors in one nephrology facility. MATERIAL AND METHODS: We conducted a three-year retrospective study on patients who underwent renal biopsy between January 2014 and December 2016. Strict written biopsy protocol was followed. Clinical and laboratory data were obtained from medical charts. Complications were categorised as minor and major, according to the need for intervention. Minor complications included macrohematuria and/or hematoma that did not require intervention. Major complications included hematuria or hematoma with fall of hematocrit that required a blood transfusion, surgery or caused death. A binary logistic regression model was used to analyse the possible factors associated with complications after the biopsy. RESULTS: We analysed 345 biopsies; samples were taken from patients aged from 15-81 years, of whom 61% were men. A total of 21 (6%) patients developed a complication, 4.4% minor and 1.7% major complications. There were no nephrectomy or death due to biopsy intervention. Overweight patients, as well as those with higher creatinine, lower hemoglobin, higher blood pressure and biopsy due to AKI had higher chances to develop complications (p = 0.037, p = 0.023, p = 0.032, p = 0.002, p = 0.002, respectively). The patients' age, gender, kidney dimension, number of passes and uninterrupted aspirin therapy were not found as significant predictors of complications. In the multivariate logistic model, body weight (OR = 1.031, 95%CI = 1.002-1.062), lower hemoglobin (OR = 0.973, 95%CI = 0.951-0.996) and hypertension (OR = 1.025, 95%CI = 1.007-1.044) increased the risk of complications in biopsied patients. CONCLUSION: Renal biopsy is a safe procedure with a low risk of complications when strict biopsy protocol is observed. Correction of anaemia and blood pressure is to be considered before the biopsy.

Predictors of Renal Dysfunction in Adults with Childhood Vesicoureteral Reflux after Long-Term Follow-Up.

BACKGROUND: Triad of childhood vesicoureteral reflux (VUR), urinary infection (UTI) and renal scarring might initiate potentially serious consequences that lead to renal dysfunction manifested at the second or third decade of life. AIM: To identify the risk factors predictive for renal dysfunction in adults with primary VUR after long-term follow-up. METHODS: We evaluated the records of 101 children (94.1% female, 5.9% male) at a median age of 5.2 ± 2.3 years (1-12 years), suffering from UTI and VUR. The patients were interviewed after mean 21 years from the first episodes of VUR (8 to 32 years). Renal function was determined from the estimated glomerular filtration rate (eGFR). RESULTS: Renal scarring was detected in 68.3% out of 82 patients and bilateral one in 7.3% patients. Linear regression analysis revealed that presence of proteinuria (B = -33.7, p=0.0001), the greater number of years from VUR diagnosis (B = -1.6, p = 0.002) and renal scarring (B = -14.8, p = 0.005) appeared as independent predictors of reduced global eGFRcreat. The same variables plus microalbuminuria (B = -1.0, p = 0.012) appeared as independent predictors of reduced global eGFRcreat-cys. Bilateral scarring (OR=25.5, p = 0.003) appeared as independent predictor of greater risk for CKD assessed using eGFRcreat while greater number of years from VUR diagnosis (OR = 1.7, p = 0.092), microalbuminuria (OR = 1.3, p = 0.047) and again bilateral scarring (OR = 31.3, p = 0.040) appeared as predictors of risk for CKD assessed using eGFRcreat-cys. CONCLUSION: Identification of those with an increased risk of progression to CKD should be the goal in all patients with childhood VUR. Their systematic follow-up should be till adulthood and older age.

Active Smoking is Associated with Lower Dialysis Adequacy in Prevalent Dialysis Patients.

BACKGROUND: Dialysis adequacy measured by single pool Kt/V (spKt/V) lower than 1.2 or urea reduction rate (URR) lower than 65% is associated with a significant increase in patient mortality rate. Patients' adherence to the medical treatment is crucial to achieve recommended targets for spKt/V. Smoking is a recognized factor of non-adherence. AIM: In this study we sought to assess the association of active smoking and dialysis adequacy. METHODS: A total of 134 prevalent dialysis patients from one dialysis center were included in an observational cross-sectional study. Clinical, laboratory and dialysis data were obtained from medical charts in previous 6 months. The number of missed, on purpose interrupted or prematurely terminated dialysis sessions was obtained. Dialysis adequacy was calculated as spKt/V and URR. Patients were questioned about current active smoking status. T-test and Chi-Square test were used for comparative analysis of dialysis adequacy with regard to smoking status. RESULTS: The majority of patients declared a non-smoking status (100 (75%)) and 34 (25%) were active smokers. Male gender, younger age and shorter dialysis vintage were significantly more often present in the active smokers ((9 (26%) vs 25 (73%), p = 0.028; 57.26 ± 12.59 vs 50.15 ± 14.10, p = 0.012; 118.59 ± 76.25 vs 88.82 ± 57.63, p = 0.030)), respectively. spKt/V and URR were significantly lower and Kt/V target was less frequently achieved in smokers ((1.46 ± 0.19 vs. 1.30 ± 0.021, p = 0.019; 67.14 ± 5.86 vs. 63.64 ± 8.30, p = 0.002; 14 (14%) vs. 11 (32%), p = 0.023), respectively. Shorter dialysis sessions, larger ultra filtrations and higher percentage of missed/interrupted dialysis session on patients' demand were observed in smokers (4.15 ± 0.30 vs. 4.05 ± 0.17, p = 0.019; 3.10 ± 0.78 vs. 3.54 ± 0.92, p = 0.017; 25 (0.3%) vs. 48 (1.8%), p = 0.031), respectively. CONCLUSION: Active smokers, especially younger men, achieve lower than the recommended levels for dialysis adequacy. Non-adherence to treatment prescription in smokers is a problem to be solved. Novel studies are recommended in patients on dialysis, to further elucidate the association of dialysis adequacy with the active smoking status.

Carnitine Palmitoyltransferase II Deficiency (CPT II) Followed By Rhabdomyolysis and Acute Kidney Injury.

BACKGROUND: Carnitine palmitoyltransferase II deficiency (CPT II) is an autosomal recessive disorder and the most common inherited disorder of mitochondrial long-chain fatty acid oxidation, characterised by attacks of myalgia and myoglobinuria. The most common "classic" myopathic form occurs in young adults and is characterised by recurrent episodes of rhabdomyolysis triggered by prolonged exercise, fasting or febrile illness. CASE PRESENTATION: We present a case of a 22-year-old Caucasian male admitted to our hospital with fever, dyspnea, fatigue, myalgia and dark urine (brown-coloured). The symptoms appeared after viral infection followed by fever. Acute kidney injury (AKI) developed as a complication, and there was a need for treatment with hemodialysis. At the clinical presentation, the patient had plasma creatine kinase (pCK) level of 130.383 U/L and plasma myoglobin level over 5000 µg/L. Genetic testing (molecular analysis) confirmed the diagnosis of inherited rhabdomyolysis, a metabolic disorder of carnitine palmitoyltransferase II deficiency. A previous episode with the same symptoms, the patient had four years ago but did not ask for medical treatment. The patient was discontinued from hemodialysis because of the resolution of acute kidney injury. The patient was discharged from the hospital in good condition, with a recommendation about his future lifestyle in order to prevent similar episodes. CONCLUSION: Every patient presenting with myalgia, dark urine (brown-coloured), high level of pCK and development of AKI requiring hemodialysis, should be explored for inherited rhabdomyolysis induced by CPT II deficiency.

The Effect of Treatment on Short-Term Outcomes in Elderly Patients with Acute Kidney Injury.

BACKGROUND: Elderly population (≥ 65) are more prone to develop acute kidney injury (AKI) compared to younger, also elderly with AKI have an increased requirement for dialysis treatment and an elevated risk of short-term and long-term mortality. AIM: The objectives of this study were to examine the effect of treatment of short-term outcomes and mortality in elderly patients with AKI. MATERIAL AND METHODS: Seventy elderly AKI patients, that filled one of the criteria of AKI definition and had hospitalization over 24 hours, were enrolled in the study. RESULTS: The median age of patients was 74.28 ± 6.64, with mean CCI (Charlson Comorbidity Index) score of 6.94 ± 1.94. The majority of patients (70%) were classified at stage 3 of AKIN, 20% of patients were classified at stage 2 and 10% at stage 1. In the groups of patients with death outcome, the chronic cardiomyopathy was more frequently present (p = 0.034). Regarding treatment, 58.6% of the AKI patients underwent hemodialysis while 41.4% received conservative treatment. Mortality rate was 52.8%, out of which 28.6% was in-hospital mortality, while in 24.3% of patients death occurred in the follow-up period of 90 days. CONCLUSION: In our study, short- term survival is not related to different treatment options. Applied treatment in elderly patients with AKI should be assessed by measuring the long term outcome.

Hypomagnesemia and cause-specific mortality in hemodialysis patients: 5-year follow-up analysis.

INTRODUCTION: The aim of this prospective study was to evaluate the association between serum magnesium (Mg) and mortality, in particular the cause-specific mortality of Mg and other risk factors in hemodialysis (HD) patients. METHODS: We studied a cohort of 185 HD patients receiving thrice-weekly HD treatment, on a dialysate Mg concentration of 0.5 mmol/L. We stratified 3 patient groups according to the level of Mg: lower (<1.1 mmol/L), intermediate-reference (1.1 to <1.3 mmol/L), and higher (Mg >1.3 mm/L). RESULTS: During the 5-year follow-up, 60 patients died, with cardiovascular (CV) disease as the predominant cause (73.3%). Hazard ratio (HR) for all-cause and CV mortality were 2.55 and 2.67 in the lower versus intermediate Mg group, but there was no significant association between the higher and intermediate Mg group. Univariate Cox regression analysis showed that Mg <1.1 versus 1.1-1.30 mml/L with HR 2.34, was a significant univariate predictor for increased mortality in addition to the Hb <110 g/L, Alb <40 g/L, C-reactive protein (CRP) ≥10 mg/L and brain natriuretic peptide >1,200 pg/mL. However, in the multivariate analysis only CRP ≥10 mg/L with HR 3.89 was a significant predictor of mortality. Subgroup analyses showed that among patients with CRP >10 mg/L, HR for all-cause and CV mortality of the lower versus intermediate Mg group were 1.96 and 2.39, respectively, not reaching significance for the higher versus intermediate Mg group. Conversely, there was no association between Mg level and all-cause and CV mortality within these 3 groups among patients with CRP <10 mg/L. CONCLUSIONS: Lower serum Mg level was significantly associated with an increased all-cause and cardiovascular mortality in HD patients, especially in inflamed patients.

Hypercalcemia as a Cause of Kidney Failure: Case Report.

BACKGROUND: Hypercalcemia is a common manifestation in clinical practice and occurs as a result of primary hyperparathyroidism, malignancy, milk-alkali syndrome, hyper or hypothyroidism, sarcoidosis and other known and unknown causes. Patients with milk-alkali syndrome typically are presented with renal failure, hypercalcemia, and metabolic alkalosis caused by the ingestion of calcium and absorbable alkali. This syndrome is caused by high intake of milk and sodium bicarbonate. CASE PRESENTATION: We present a 28-year old male admitted to hospital with a one-month history of nausea, vomiting, epigastric pain, increased blood pressure and worsening of renal function with hypercalcemia. His serum PTH level was almost undetectable; he had mild alkalosis, renal failure with eGFR of 42 ml/min, anemia, hypertension and abnormal ECG with shortened QT interval and ST elevation in V1-V4. He had a positive medical history for calcium-containing antacids intake and after ruling out primary hyperparathyroidism, malignancy, multiple myelomas, sarcoidosis, and thyroid dysfunction, it seemed plausible to diagnose him as having the milk-alkali syndrome. CONCLUSION: Although milk-alkali syndrome currently may be more probably a result of calcium and vitamin D intake in postmenopausal women, or in elderly men with reduced kidney function taking calcium-containing medications, one should not exclude the possibility of its appearance in younger patients taking calcium-containing medications and consider it a serious condition taking into account its possibility of inducing renal insufficiency.

Timing of nephrology referral and initiation of dialysis as predictors for survival in hemodialysis patients: 5-year follow-up analysis.

BACKGROUND: A consensus about the optimal timing of dialysis initiation is still controversial. Thus, the goal of this analysis was to compare outcomes in patients with early and late referral with early and late initiation of hemodialysis (HD). METHODS: We studied 190 patients (mean age 52.03±14.22) who were initiated on HD between 1994 and 2004. Patients who received regular nephrology care during 12 months before HD initiation were categorized as early referrals (ER) and those without nephrology care were late referrals (LR). The early start (E-start) was defined by the estimated GFR (eGFR) at start of HD≥7.5 mL/min/1.73 m2, and the late start (L-start) by eGFR of <7.5 mL/min/1.73 m2. The four groups of patients (ER with E-start and L-start; LR with E-start and L-start) were prospectively followed in the next 60 months after HD initiation. RESULTS: During the follow-up, 43.3% of E-start and 43.2% of L-start patients died, without significant difference in survival between the groups [HR for L-start vs. E-start=1.06 (95% CI 0.69-1.62); p=0.797]. When survival between ER and LR groups was compared (28.1% patients in the ER and 53.2% in the LR died), there was significant difference in survival [HR for LR vs. ER=2.16 (95% CI 1.28-3.65); p=0.004]. Compared with patients with ER and L-start, higher mortality was observed among those with LR and L-start [HR 3.51 (95% CI 1.48-8.35); p=0.004] and LR with E-start [HR 2.79 (95% CI 1.16-6.7); p=0.022]. There was no significant difference between patients in ER with L-start and ER with E-start. CONCLUSIONS: Our study showed that ER above 12 months before HD initiation and L-start of dialysis was associated with a reduced mortality risk in HD patients.

Does hepatitis C increase the accumulation of advanced glycation end products in haemodialysis patients?

BACKGROUND: Hepatitis C may cause increased levels of oxidative stress that contribute to accumulation of advanced glycation end products (AGEs), which increase the risk of cardiovascular disease (CVD). The aim of this study was to determine the influence of hepatitis C on AGE accumulation in haemodialysis patients. METHODS: AGE accumulation was measured by means of skin autofluorescence (AF) in 92 haemodialysis (HD) patients and 93 age-matched healthy controls. In the HD patients, CVD-related biochemical variables were also measured. The HD patients were tested for hepatitis C virus (HCV) antibodies and allocated to a HCV+ or HCV- group. RESULTS: Skin AF of the healthy subjects was lower than skin AF in the HD patients (3.13 +/- 0.95 vs 2.2 +/- 0.47; P < 0.001). We calculated the average increase of skin AF in the healthy subjects to be 0.017 arbitrary units per year, being 14 times lower than in HD patients with CVD only and 20 times lower than in HD patients suffering from combined CVD and diabetes mellitus (DM). Multivariate regression analysis showed that AGE accumulation in HD patients can be described by the independent effects of age, DM, CVD and HD vintage. Although inter-cellular adhesion molecule 1 and liver enzymes were elevated in HCV+ HD patients, levels of oxidative stress markers and skin AF were not significantly different between HCV+ and HCV- HD patients. CONCLUSIONS: AGE accumulation was higher in the HD patients than in the healthy controls. AGE accumulation did not differ in HCV+ and HCV- HD patients. This might be due to the fact that hepatitis C did not cause oxidative stress in our HD population. Independent markers of AGE accumulation were age, HD vintage, DM and CVD, but not hepatitis C.

Long-term follow up of sustained viral response after treatment of hepatitis C with pegylated interferon alpha-2a in hemodialysis patients.

PURPOSE: The aim of this study was to evaluate the persistence of sustained viral response after treatment of hepatitis C with pegylated interferon alpha-2a in hemodialysis patients. METHODS: 14 hemodialysis patients with chronic hepatitis C were treated with pegylated interferon alpha-2a for a period of 48 weeks. Achieved sustained viral response rate was 35.7% (5/14 patients) at week 72, i.e. 24 weeks after the treatment ended. All treated patients were then prospectively followed until week 144. Follow-up viral data, such as HCV antibodies, serum HCV RNA, and HCV RNA genotype, were determined at week 96 and week 144. HCV antibodies were determined by a 3rd-generation ELISA assay. The presence of HCV RNA was determined using reverse transcriptase polymerase chain reaction (AMPLICOR Hepatitis C Virus Test). HCV genotype was analyzed by reverse transcriptase polymerase chain reaction followed by hybridization of amplified products. The biochemical data were recorded every 24 weeks during the follow-up period. RESULTS: The 5 patients (35.7%), who achieved sustained viral response (SVR), remained HCV RNA negative at week 96. At week 144, 4 hemodialysis patients (28.6%) remained HCV RNA negative. There was a relapse of HCV infection in 1 patient after week 96 of the study. The patients who remained HCV RNA negative also maintained the achieved biochemical response throughout the follow-up period. CONCLUSION: Long-term follow-up of treated hemodialysis patients with pegylated interferon alpha-2a showed persistence of the sustained viral and biochemical response.

Improvement of bone and mineral parameters related to adynamic bone disease by diminishing dialysate calcium.

BACKGROUND: The existence of adynamic bone disease (ABD) as most prevalent form of renal osteodystrophy in recent years and its reduced ability to handle an exogenous calcium load has implied a higher risk for vascular and soft-tissue calcifications. The effect of low dialysate calcium (LCD) on parathyroid hormone (PTH) secretion in ABD patients has not yet sufficiently been clarified. This randomized, prospective study aimed to compare the effects of LCD and high calcium dialysate (HCD) on the evolution of bone and mineral parameters related to ABD in dialysis patients. METHODS: 52 out of 60 patients with predialysis intact PTH<100 pg/ml completed this study and were equally distributed over LCD (1.25 mmol/l) or HCD (1.75 mmol/l) treatment. The duration of the study was 6 months and the only peroral phosphate binder administered was calcium carbonate. Total and ionised calcium were measured monthly in serum before and after dialysis while serum parameters relevant to bone were measured at the enrollment and at 3-month intervals. RESULTS: There were no differences in predialysis mean phosphate or calcium x phosphorus product (Ca x P). The most common side effects of both treatments were comparable. Hypotension occurred in 16% and 17% and cramps in 6% and 8% of the dialysis sessions, in the HCD and LCD group, respectively. The groups did not differ in the mean tCa before dialysis, but this parameter was significantly higher in the HCD group vs. LCD at the end of dialysis (2.59+/-0.18 vs. 2.44+/-0.19 mmol/l; p<0.01). The patients of the HCD group also had a significantly higher mean iCa both before (1.08+/-0.05 vs. 1.04+/-0.06 mmol/l; p=0.02) and at the end of dialysis (1.18+/-0.04 vs. 1.48+/-0.04 mmol/l; p<0.01). There were no differences within the LCD group between baseline and end of dialysis treatment values of tCa and iCa. However, the mean tCa and iCa were markedly increased at the end of dialysis in the HDC group [2.40+/-0.21 vs. 2.59+/-0.18 mmol/l (p<0.01); 1.08+/-0.05 vs. 1.18+/-0.04 mmol/l (p<0.01)]. Mean serum levels of iPTH and total alkaline phosphatase in the LCD group were increased at 3 months and at the end of the study compared with the baseline levels [(38.6+/-22.9 vs. 63.3+/-46.0 vs. 78.6+/-44.7 pg/ml); (59.5+/-18.7 vs. 75.9+/-26.7 vs. 84.0+/-35.4 U/l)], respectively, and bone alkaline phosphatase increased also only after 6 months of treatment (23.4+/-7.3 U/l vs. 35.6+/-22.3). The bone markers in the HCD group did not change. At the end of the study all bone parameters in the LCD group were significantly higher than in the HCD group. CONCLUSION: There was an evolution towards parameters reflecting higher bone turnover in patients treated with dialysate calcium of 1.25 mmol/l, probably by prevention of a positive calcium balance and enabling sustained stimulation of PTH secretion. Hence, LCD might be considered a valuable therapeutic option for ABD patients.