Autosomal dominant polycystic kidney disease in hemodialysis patients in southern Brazil

Introduction: Autosomal dominant polycystic kidney disease is the most common hereditary renal disease in humans. Objective: To examine the prevalence, clinical and laboratory characteristics of patients with polycystic kidneys and relate disease manifestations by gender. Methods: This was an observational and retrospective study. All the medical records of patients with polycystic kidneys who initiated hemodialysis between 1995 and 2012, in four centers that treat patients of the coverage area of the 15th regional health Paraná (Brazil), were analyzed. Results: The study included 48 patients with polycystic kidneys, the primary cause of stage 5 CKD. Disease prevalence was one in 10,912 people. The average age of dialysis initiation was 50.7 years and the follow-up time on dialysis until transplantation (36.5 months) was lower among men. Hypertension was the most frequent diagnosis in 73% of patients, predominantly in women (51.4%). The liver cyst was the most frequent extrarenal manifestations in men (60.0%). The death occurred in 10.4% of patients using hemodialysis, and 60% of men. The class of antihypertensive drug used was that acts on the renin-angiotensin system with higher frequency of use among women (53.3%). The post-dialysis urea was significantly higher in men. Conclusion: The prevalence of the disease is low among hemodialysis patients in southern Brazil. The differences observed between genders, with the exception of the post-dialysis urea, were not significant. The findings are different from those reported in North America and Europe.

The phylogeography of salmonid proliferative kidney disease in Europe and North America

Salmonid proliferative kidney disease (PKD) is caused by the myxozoan Tetracapsuloides bryosalmonae. Given the serious and apparently growing impact of PKD on farmed and wild salmonids, we undertook a phylogeographic study to gain insights into the history of genealogical lineages of T. bryosalmonae in Europe and North America, and to determine if the global expansion of rainbow trout farming has spread the disease. Phylogenetic analyses of internal transcribed spacer 1 sequences revealed a clade composed of all North American sequences plus a subset of Italian and French sequences. High genetic diversity in North America and the absence of genotypes diagnostic of the North American clade in the rest of Europe imply that southern Europe was colonized by immigration from North America; however, sequence divergence suggests that this colonization substantially pre-dated fisheries activities. Furthermore, the lack of southern European lineages in the rest of Europe, despite widespread rainbow trout farming, indicates that T. bryosalmonae is not transported through fisheries activities. This result strikingly contrasts with the commonness of fisheries-related introductions of other pathogens and parasites and indicates that fishes may be dead-end hosts. Our results also demonstrate that European strains of T. bryosalmonae infect and induce PKD in rainbow trout introduced to Europe.

Infection of bryozoans by Tetracapsuloides bryosalmonae at sites endemic for salmonid proliferative kidney disease

Laboratory-reared colonies of the bryozoans Fredericella sultana and Plumatella fungosa were placed upstream of 2 fish farms endemic for salmonid proliferative kidney disease (PKD) to assess rates of infection of bryozoans by Tetra caps uloides bryosalmonae, the causative agent of PKD. Colonies were deployed in the field for 8 trial periods of 2 wk each throughout the summer of 2001. Following each trial, bryozoan colonies were maintained in laboratory culture for 28 d and were regularly monitored for infection by searching for sac stages of T bryosalmonae. Infections were never identified by observations of sac stages, however positive PCR results and sequencing of cultured material confirmed that cryptic infections were present in colonies of both species deployed at one site. The possibility that PCR results reflected contamination of surfaces of bryozoans can be excluded, given the short period of spore viability of T bryosalmonae. Highest rates of infection occurred when 4 of 23 colonies of F sultana and 1 of 12 colonies of P. fungosa were infected during the period 10 to 24 July. No infections were detected from mid-August to late October at this site. None of the colonies at the other site became infected throughout the period of study. Our data provide the first estimates of infection rates of bryozoans by T bryosalmonae. Additionally, they provide evidence that a cryptic stage can be maintained within bryozoan hosts for a period of 4 to 6 wk.

Factors associated with health-related quality of life after successful kidney transplantation: a population-based study

Kidney transplantation improves the quality of life of end-stage renal disease patients. The quality of life benefits, however, pertain to patients on average, not to all transplant recipients. The aim of this study was to identify factors associated with health-related quality of life after kidney transplantation. Population-based study with a cross-sectional design was carried out and quality of life was assessed by SF-36 Health Survey Version 1. A multivariate linear regression model was constructed with sociodemographic, clinical and laboratory data as independent variables. Two hundred and seventy-two kidney recipients with a functioning graft were analyzed. Hypertension, diabetes, higher serum creatinine and lower hematocrit were independently and significantly associated with lower scores for the SF-36 oblique physical component summary (PCSc). The final regression model explained 11% of the PCSc variance. The scores of oblique mental component summary (MCSc) were worse for females, patients with a lower income, unemployed and patients with a higher serum creatinine. The regression model explained 9% of the MCSc variance. Among the studied variables, comorbidity and graft function were the main factors associated with the PCSc, and sociodemographic variables and graft function were the main determinants of MCSc. Despite comprehensive, the final regression models explained only a little part of the heath-related quality of life variance. Additional factors, such as personal, environmental and clinical ones might influence quality of life perceived by the patients after kidney transplantation.

Calciphylaxis: a rare but potentially fatal event of chronic kidney disease. Case report

Calciphylaxis or calcific uremic arteriolopathy is a rare cutaneous-systemic disease occurring in patients with advanced chronic kidney disease. The classical clinical picture is that of a necrotic and progressive skin ulcer of reticular pattern, mostly in the lower legs and susceptible to local infection. It is a product of mural calcification and occlusion of cutaneous and sub-cutaneous arteries and arterioles. The authors report the case of a 73-year-old male patient in his late stage of renal disease presenting severe necrotic cutaneous ulcers on lower legs followed by local and systemic infection and death due to sepse after parathyroidectomy.

Long-Term Follow-Up of Patients after Acute Kidney Injury: Patterns of Renal Functional Recovery

Background and Objectives: Patients who survive acute kidney injury (AKI), especially those with partial renal recovery, present a higher long-term mortality risk. However, there is no consensus on the best time to assess renal function after an episode of acute kidney injury or agreement on the definition of renal recovery. In addition, only limited data regarding predictors of recovery are available. Design, Setting, Participants, & Measurements: From 1984 to 2009, 84 adult survivors of acute kidney injury were followed by the same nephrologist (RCRMA) for a median time of 4.1 years. Patients were seen at least once each year after discharge until end stage renal disease (ESRD) or death. In each consultation serum creatinine was measured and glomerular filtration rate estimated. Renal recovery was defined as a glomerular filtration rate value >= 60 mL/min/1.73 m2. A multiple logistic regression was performed to evaluate factors independently associated with renal recovery. Results: The median length of follow-up was 50 months (30-90 months). All patients had stabilized their glomerular filtration rates by 18 months and 83% of them stabilized earlier: up to 12 months. Renal recovery occurred in 16 patients (19%) at discharge and in 54 (64%) by 18 months. Six patients died and four patients progressed to ESRD during the follow up period. Age (OR 1.09, p < 0.0001) and serum creatinine at hospital discharge (OR 2.48, p = 0.007) were independent factors associated with non renal recovery. The acute kidney injury severity, evaluated by peak serum creatinine and need for dialysis, was not associated with non renal recovery. Conclusions: Renal recovery must be evaluated no earlier than one year after an acute kidney injury episode. Nephrology referral should be considered mainly for older patients and those with elevated serum creatinine at hospital discharge.

Lithiasis in 1,313 Kidney Transplants: Incidence, Diagnosis, and Management

Background. Renal transplantation remains the optimal treatment of patients with end-stage renal disease. Urinary lithiasis represents an unusual urologic complication in renal transplantation, with an incidence of <1%. Today, recipients of kidneys from deceased donors are more likely to receive grafts with undiagnosed lithiasis, which does not occur in patients from living donors, owing to screening with computerized tomography. Objective. The aim of this study was to evaluate the incidence, diagnosis, and therapeutic management of renal lithiasis in transplanted kidneys at a single institution. Methods. We reviewed the medical records for 1,313 patients who underwent kidney transplantation from February 1968 to February 2011. Results. Among the grafts, 17 patients (1.29%) had nephrolithiasis: 9 women and 8 men. Ages ranged from 32 to 63 years (mean = 45.6 years). Fifteen patients received kidneys from cadaveric and only 2 from living related donors. Two stones, both located inside the ureter, were identified during transplant surgery (11.7%). Three instances of lithiasis were incidentally diagnosed by ultrasound during graft evaluation, within 7 days after surgery (17.6%); all 3 were in the calyces. The 12 remaining patients had the stones diagnosed later (70.58%): 6 in the calyces, 3 in the renal pelvis, and 3 inside the ureter. Conclusions. Urinary lithiasis is a rare complication in renal transplantation. In most patients the condition occurs without pain. The diagnosis and treatment options for graft urolithiasis are similar to those patients with nephrofithiasis in the general population. Extracorporeal shock wave lithotripsy (ESWL) was the most common treatment method.

Can we predict which patients will evolve to chronic kidney disease after nephrectomy for cortical renal tumors?

Introduction: While some studies show that patients submitted to radical nephrectomy have a higher risk of developing chronic kidney disease (CKD), some studies report that carefully selected living kidney donors do not present a higher risk for CKD. Here, we aim to study predictive factors of CKD after radical nephrectomy. Materials and Methods: Between January 2006 to January 2010, 107 patients submitted to radical nephrectomy for cortical renal tumors at our institution were enrolled in this study. Demographic data were recorded, modified Charlson-Romano Index was calculated, and creatinine clearance was estimated using abbreviated Modification of Diet in Renal Disease (MDRD) study equation. Pathological characteristics, surgical access and surgical complications were also reviewed. The end-point of the current study was new onset estimated glomerular filtration rate (eGFR) less than 60 and less than 45 mL/minute/1.73 m(2). Results: Age, preoperative eGFR, Charlson-Romano Index and hypertension were predictive factors of renal function loss, when the end-point considered was eGFR lower than 60 mL/minute/1.73 m(2). Age and preoperative eGFR were predictive factors of renal function loss, when the end-point considered was eGFR lower than 45 mL/minute/1.73 m2. Moreover, each year older increased 1.1 times the risk of eGFR lower than 60 and 45 mL/minute/1.73 m(2). After multivariate logistic regression, only age remained as an independent predictive factor of eGFR loss. Conclusion: Age is an independent predictive factor of GFR loss for patients submitted to radical nephrectomy for cortical renal tumors.

Progenitori endoteliali nei pazienti con Chronic Kidney Disease - Mineral and Bone Disorder (CKD-MBD) in fase uremica: effetti del trattamento con vitamina D.

L'insufficienza renale cronica (CKD) è associata ad un rischio cardiovascolare più elevato rispetto alla popolazione generale: fattori come uremia, stress ossidativo, età dialitica, infiammazione, alterazioni del metabolismo minerale e presenza di calcificazioni vascolari incidono fortemente sulla morbosità e mortalità per cause cardiovascolari nel paziente uremico. Diversi studi hanno verificato il coinvolgimento dei progenitori endoteliali (EPC) nella malattia aterosclerotica ed è stato dimostrato che esprimono osteocalcina, marcatore di calcificazione. Inoltre, nella CKD è presente una disfunzione in numero e funzionalità delle EPC. Attualmente, il ruolo delle EPC nella formazione delle calcificazioni vascolari nei pazienti in dialisi non è stato ancora chiarito. Lo scopo della tesi è quello di studiare le EPC prelevate da pazienti con CKD, al fine di determinarne numero e fenotipo. È stato anche valutato l'effetto del trattamento in vitro e in vivo con calcitriolo e paracalcitolo sulle EPC, dato il deficit di vitamina D dei pazienti con CKD: il trattamento con vitamina D sembra avere effetti positivi sul sistema cardiovascolare. Sono stati valutati: numero di EPC circolanti e la relativa espressione di osteocalcina e del recettore della vitamina D; morfologia e fenotipo EPC in vitro; effetti di calcitriolo e paracalcitolo sull’espressione di osteocalcina e sui depositi di calcio. I risultati dello studio suggeriscono che il trattamento con vitamina D abbia un effetto positivo sulle EPC, aumentando il numero di EPC circolanti e normalizzandone la morfologia. Sia calcitriolo che paracalcitolo sono in grado di ridurre notevolmente l’espressione di OC, mentre solo il paracalcitolo ha un effetto significativo sulla riduzione dei depositi di calcio in coltura. In conclusione, il trattamento con vitamina D sembra ridurre il potenziale calcifico delle EPC nell’uremia, aprendo nuove strade per la gestione del rischio cardiovascolare nei pazienti affetti da CKD.

Mapping of a new locus for congenital anomalies of the kidney and urinary tract on chromosome 8q24

Congenital anomalies of the kidney and urinary tract (CAKUT) account for the majority of end-stage renal disease in children (50%). Previous studies have mapped autosomal dominant loci for CAKUT. We here report a genome-wide search for linkage in a large pedigree of Somalian descent containing eight affected individuals with a non-syndromic form of CAKUT.

Quantitative assessment of urea generation and elimination in healthy dogs and in dogs with chronic kidney disease

BACKGROUND: Kinetic assessment of urea, the main end product of protein metabolism, could serve to assess protein catabolism in dogs with chronic kidney disease (CKD). Protein malnutrition and catabolism are poorly documented in CKD and they often are neglected clinically because of a lack of appropriate evaluation tools. HYPOTHESIS: Generation and excretion of urea are altered in dogs with CKD. ANIMALS: Nine dogs with spontaneous CKD (IRIS stages 2-4) and 5 healthy research dogs. METHODS: Endogenous renal clearance (Clrenal) of urea and creatinine was measured first. Exogenous plasma clearance (Clplasma, total body clearance) of the 2 markers then was determined by an IV infusion of urea (250-1,000 mg/kg over 20 minutes) and an IV bolus of creatinine (40 mg/kg). Extrarenal clearance (Clextra) was defined as the difference between Clplasma)and Clrenal. Endogenous urea generation was computed assuming steady-state conditions. RESULTS: Median Clrenal and Clextra of urea were 2.17 and 0.21 mL/min/kg in healthy dogs and 0.37 and 0.28 mL/min/kg in CKD dogs. The proportion of urea cleared by extrarenal route was markedly higher in dogs with glomerular filtration rate<1 mL/kg/min than in normal dogs, reaching up to 85% of the total clearance. A comparable pattern was observed for creatinine excretion, except in 1 dog, Clextra remained<20% of Clplasma. CONCLUSION: Extrarenal pathways of urea excretion are predominant in dogs with advanced CKD and justify exploring adjunctive therapies based on enteric nitrogen excretion in dogs. A trend toward increased urea generation may indicate increased catabolism in advanced CKD.

Cardiorenal End Points in a Trial of Aliskiren for Type 2 Diabetes

BACKGROUND: This study was undertaken to determine whether use of the direct renin inhibitor aliskiren would reduce cardiovascular and renal events in patients with type 2 diabetes and chronic kidney disease, cardiovascular disease, or both. METHODS: In a double-blind fashion, we randomly assigned 8561 patients to aliskiren (300 mg daily) or placebo as an adjunct to an angiotensin-converting-enzyme inhibitor or an angiotensin-receptor blocker. The primary end point was a composite of the time to cardiovascular death or a first occurrence of cardiac arrest with resuscitation; nonfatal myocardial infarction; nonfatal stroke; unplanned hospitalization for heart failure; end-stage renal disease, death attributable to kidney failure, or the need for renal-replacement therapy with no dialysis or transplantation available or initiated; or doubling of the baseline serum creatinine level. RESULTS: The trial was stopped prematurely after the second interim efficacy analysis. After a median follow-up of 32.9 months, the primary end point had occurred in 783 patients (18.3%) assigned to aliskiren as compared with 732 (17.1%) assigned to placebo (hazard ratio, 1.08; 95% confidence interval [CI], 0.98 to 1.20; P=0.12). Effects on secondary renal end points were similar. Systolic and diastolic blood pressures were lower with aliskiren (between-group differences, 1.3 and 0.6 mm Hg, respectively) and the mean reduction in the urinary albumin-to-creatinine ratio was greater (between-group difference, 14 percentage points; 95% CI, 11 to 17). The proportion of patients with hyperkalemia (serum potassium level, ≥6 mmol per liter) was significantly higher in the aliskiren group than in the placebo group (11.2% vs. 7.2%), as was the proportion with reported hypotension (12.1% vs. 8.3%) (P<0.001 for both comparisons). CONCLUSIONS: The addition of aliskiren to standard therapy with renin-angiotensin system blockade in patients with type 2 diabetes who are at high risk for cardiovascular and renal events is not supported by these data and may even be harmful. (Funded by Novartis; ALTITUDE ClinicalTrials.gov number, NCT00549757.).

Successful kidney transplantation from donor with Marfan's syndrome

Marfan's syndrome is caused by mutations in the extracellular matrix protein fibrillin-1 with aortic aneurysm and dissection being its most life-threatening manifestations. Kidney transplantation from donors with Marfan's syndrome has never been reported in the literature, possibly because of reticences due to the underlying connective tissue disease. Here, we report two patients with end-stage renal disease, transplanted with the kidneys from a donor with Marfan's syndrome who died of aortic dissection and cerebral hemorrhage. After delayed graft function in both recipients, renal function normalized with no renovascular complications and negative proteinuria for 6 years in one patient and 2 years in the other patient, who died from an ischemic cerebrovascular insult. Kidneys from organ donors with Marfan's syndrome might be suitable for transplantation.

Risk of acute kidney injury in patients with severe aortic valve stenosis undergoing transcatheter valve replacement

BACKGROUND: Transcatheter aortic valve implantation (TAVI) for high-risk and inoperable patients with severe aortic stenosis is an emerging procedure in cardiovascular medicine. Little is known of the impact of TAVI on renal function. METHODS: We analysed retrospectively renal baseline characteristics and outcome in 58 patients including 2 patients on chronic haemodialysis undergoing TAVI at our institution. Acute kidney injury (AKI) was defined according to the RIFLE classification. RESULTS: Fifty-eight patients with severe symptomatic aortic stenosis not considered suitable for conventional surgical valve replacement with a mean age of 83 +/- 5 years underwent TAVI. Two patients died during transfemoral valve implantation and two patients in the first month after TAVI resulting in a 30-day mortality of 6.9%. Vascular access was transfemoral in 46 patients and transapical in 12. Estimated glomerular filtration rate (eGFR) increased in 30 patients (56%). Fifteen patients (28%) developed AKI, of which four patients had to be dialyzed temporarily and one remained on chronic renal replacement therapy. Risk factors for AKI comprised, among others, transapical access, number of blood transfusions, postinterventional thrombocytopaenia and severe inflammatory response syndrome (SIRS). CONCLUSIONS: TAVI is feasible in patients with a high burden of comorbidities and in patients with pre-existing end-stage renal disease who would be otherwise not considered as candidates for conventional aortic valve replacement. Although GFR improved in more than half of the patients, this benefit was associated with a risk of postinterventional AKI. Future investigations should define preventive measures of peri-procedural kidney injury.

Effects of deflazacort versus prednisone on bone mass, body composition, and lipid profile: a randomized, double blind study in kidney transplant patients

To compare the effects of deflazacort (DEFLA) vs. prednisone (PRED) on bone mineral density (BMD), body composition, and lipids, 24 patients with end-stage renal disease were randomized in a double blind design and followed 78 weeks after kidney transplantation. BMD and body composition were assessed using dual energy x-ray absorptiometry. Seventeen patients completed the study. Glucocorticosteroid doses, cyclosporine levels, rejection episodes, and drop-out rates were similar in both groups. Lumbar BMD decreased more in PRED than in DEFLA (P < 0.05), the difference being particularly marked after 24 weeks (9.1 +/- 1.8% vs. 3.0 +/- 2.4%, respectively). Hip BMD decreased from baseline in both groups (P < 0.01), without intergroup differences. Whole body BMD decreased from baseline in PRED (P < 0.001), but not in DEFLA. Lean body mass decreased by approximately 2.5 kg in both groups after 6-12 weeks (P < 0.001), then remained stable. Fat mass increased more (P < 0.01) in PRED than in DEFLA (7.1 +/- 1.8 vs. 3.5 +/- 1.4 kg). Larger increases in total cholesterol (P < 0.03), low density lipoprotein cholesterol (P < 0.01), lipoprotein B2 (P < 0.03), and triglycerides (P = 0.054) were observed in PRED than in DEFLA. In conclusion, using DEFLA instead of PRED in kidney transplant patients is associated with decreased loss of total skeleton and lumbar spine BMD, but does not alter bone loss at the upper femur. DEFLA also helps to prevent fat accumulation and worsening of the lipid profile.