Religious/spiritual coping in people with chronic kidney disease undergoing hemodialysis

The objective of the present study is to investigate the use of religious/spiritual coping mechanisms in patients with chronic kidney disease undergoing hemodialysis, by means of interviews using a sociodemographic questionnaire and the religious/spiritual coping scale. Data analysis was performed using descriptive statistics and multiple linear regression. A total of 123 individuals were interviewed, 79.6% of whom presented a high score for religious/spiritual coping and none of whom presented low or irrelevant scores. The variables that affected the religious/spiritual coping behavior were: gender, age group, treatment time, family income, and religious practice. In conclusion, the participants used religious/spiritual coping mechanisms as a strategy to cope with the disease, particularly women with a higher family income who attend church every week.

Repression of osteocyte Wnt/beta-catenin signaling is an early event in the progression of renal osteodystrophy

Chronic kidney diseasemineral bone disorder (CKD-MBD) is defined by abnormalities in mineral and hormone metabolism, bone histomorphometric changes, and/or the presence of soft-tissue calcification. Emerging evidence suggests that features of CKD-MBD may occur early in disease progression and are associated with changes in osteocyte function. To identify early changes in bone, we utilized the jck mouse, a genetic model of polycystic kidney disease that exhibits progressive renal disease. At 6 weeks of age, jck mice have normal renal function and no evidence of bone disease but exhibit continual decline in renal function and death by 20 weeks of age, when approximately 40% to 60% of them have vascular calcification. Temporal changes in serum parameters were identified in jck relative to wild-type mice from 6 through 18 weeks of age and were subsequently shown to largely mirror serum changes commonly associated with clinical CKD-MBD. Bone histomorphometry revealed progressive changes associated with increased osteoclast activity and elevated bone formation relative to wild-type mice. To capture the early molecular and cellular events in the progression of CKD-MBD we examined cell-specific pathways associated with bone remodeling at the protein and/or gene expression level. Importantly, a steady increase in the number of cells expressing phosphor-Ser33/37-beta-catenin was observed both in mouse and human bones. Overall repression of Wnt/beta-catenin signaling within osteocytes occurred in conjunction with increased expression of Wnt antagonists (SOST and sFRP4) and genes associated with osteoclast activity, including receptor activator of NF-?B ligand (RANKL). The resulting increase in the RANKL/osteoprotegerin (OPG) ratio correlated with increased osteoclast activity. In late-stage disease, an apparent repression of genes associated with osteoblast function was observed. These data confirm that jck mice develop progressive biochemical changes in CKD-MBD and suggest that repression of the Wnt/beta-catenin pathway is involved in the pathogenesis of renal osteodystrophy. (C) 2012 American Society for Bone and Mineral Research.

The role of myocardial scintigraphy in the assessment of cardiovascular risk in patients with end-stage chronic kidney disease on the waiting list for renal transplantation

The usefulness of stress myocardial perfusion scintigraphy for cardiovascular (CV) risk stratification in chronic kidney disease remains controversial. We tested the hypothesis that different clinical risk profiles influence the test. We assessed the prognostic value of myocardial scintigraphy in 892 consecutive renal transplant candidates classified into four risk groups: very high (aged epsilon 50 years, diabetes and CV disease), high (two factors), intermediate (one factor) and low (no factor). The incidence of CV events and death was 20 and 18, respectively (median follow-up 22 months). Altered stress testing was associated with an increased probability of cardiovascular events only in intermediate-risk (one risk factor) patients [30.3 versus 10, hazard ratio (HR) 2.37, confidence interval (CI) 1.693.33, P 0.0001]. Low-risk patients did well regardless of scan results. In patients with two or three risk factors, an altered stress test did not add to the already increased CV risk. Myocardial scintigraphy was related to overall mortality only in intermediate-risk patients (HR 2.8, CI 1.55.1, P 0.007). CV risk stratification based on myocardial stress testing is useful only in patients with just one risk factor. Screening may avoid unnecessary testing in 60 of patients, help stratifying for risk of events and provide an explanation for the inconsistent performance of myocardial scintigraphy.

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.

Life cycle complexity, environmental change and the emerging status of salmonid proliferative kidney disease

P>1. Proliferative kidney disease (PKD) is a disease of salmonid fish caused by the endoparasitic myxozoan, Tetracapsuloides bryosalmonae, which uses freshwater bryozoans as primary hosts. Clinical PKD is characterised by a temperature-dependent proliferative and inflammatory response to parasite stages in the kidney.;2. Evidence that PKD is an emerging disease includes outbreaks in new regions, declines in Swiss brown trout populations and the adoption of expensive practices by fish farms to reduce heavy losses. Disease-related mortality in wild fish populations is almost certainly underestimated because of e.g. oversight, scavenging by wild animals, misdiagnosis and fish stocking.;3. PKD prevalences are spatially and temporally variable, range from 0 to 90-100% and are typically highest in juvenile fish.;4. Laboratory and field studies demonstrate that (i) increasing temperatures enhance disease prevalence, severity and distribution and PKD-related mortality; (ii) eutrophication may promote outbreaks. Both bryozoans and T. bryosalmonae stages in bryozoans undergo temperature- and nutrient-driven proliferation.;5. Tetracapsuloides bryosalmonae is likely to achieve persistent infection of highly clonal bryozoan hosts through vertical transmission, low virulence and host condition-dependent cycling between covert and overt infections. Exploitation of fish hosts entails massive proliferation and spore production by stages that escape the immune response. Many aspects of the parasite's life cycle remain obscure. If infectious stages are produced in all hosts then the complex life cycle includes multiple transmission routes.;6. Patterns of disease outbreaks suggest that background, subclinical infections exist under normal environmental conditions. When conditions change, outbreaks may then occur in regions where infection was hitherto unsuspected.;7. Environmental change is likely to cause PKD outbreaks in more northerly regions as warmer temperatures promote disease development, enhance bryozoan biomass and increase spore production, but may also reduce the geographical range of this unique multihost-parasite system. Coevolutionary dynamics resulting from host-parasite interactions that maximise fitness in previous environments may pose problems for sustainability, particularly in view of extensive declines in salmonid populations and degradation of many freshwater habitats.

A deletion in the N-myc downstream regulated gene 1 (NDRG1) gene in Greyhounds with polyneuropathy

The polyneuropathy of juvenile Greyhound show dogs shows clinical similarities to the genetically heterogeneous Charcot-Marie-Tooth (CMT) disease in humans. The pedigrees containing affected dogs suggest monogenic autosomal recessive inheritance and all affected dogs trace back to a single male. Here, we studied the neuropathology of this disease and identified a candidate causative mutation. Peripheral nerve biopsies from affected dogs were examined using semi-thin histology, nerve fibre teasing and electron microscopy. A severe chronic progressive mixed polyneuropathy was observed. Seven affected and 17 related control dogs were genotyped on the 50k canine SNP chip. This allowed us to localize the causative mutation to a 19.5 Mb interval on chromosome 13 by homozygosity mapping. The NDRG1 gene is located within this interval and NDRG1 mutations have been shown to cause hereditary motor and sensory neuropathy-Lom in humans (CMT4D). Therefore, we considered NDRG1 a positional and functional candidate gene and performed mutation analysis in affected and control Greyhounds. A 10 bp deletion in canine NDRG1 exon 15 (c.1080_1089delTCGCCTGGAC) was perfectly associated with the polyneuropathy phenotype of Greyhound show dogs. The deletion causes a frame shift (p.Arg361SerfsX60) which alters several amino acids before a stop codon is encountered. A reduced level of NDRG1 transcript could be detected by RT-PCR. Western blot analysis demonstrated an absence of NDRG1 protein in peripheral nerve biopsy of an affected Greyhound. We thus have identified a candidate causative mutation for polyneuropathy in Greyhounds and identified the first genetically characterized canine CMT model which offers an opportunity to gain further insights into the pathobiology and therapy of human NDRG1 associated CMT disease. Selection against this mutation can now be used to eliminate polyneuropathy from Greyhound show dogs.

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.

Proliferative kidney disease in rainbow trout: time- and temperature-related renal pathology and parasite distribution

Proliferative kidney disease is a parasitic infection of salmonid fishes caused by Tetracapsuloides bryosalmonae. The main target organ of the parasite in the fish is the kidney. To investigate the influence of water temperature on the disease in fish, rainbow trout Oncorhynchus mykiss infected with T bryosalmonae were kept at 12 degrees C and 18 degrees C. The number of parasites, the type and degree of lesions in the kidney and the mortality rate was evaluated from infection until full development of disease. While mortality stayed low at 12 degrees C, it reached 77% at 18 degrees C. At 12 degrees C, pathological lesions were dominated by a multifocal proliferative and granulomatous interstitial nephritis. This was accompanied by low numbers of T. bryosalmonae, mainly located in the interstitial lesions. With progression of the disease, small numbers of parasites appeared in the excretory tubuli, and parasite DNA was detected in the urine. Parasite degeneration in the interstitium was observed at late stages of the disease. At 18 degrees C, pathological lesions in kidneys were more severe and more widely distributed, and accompanied by significantly higher parasite numbers. Distribution of parasites in the renal compartments, onset of parasite degeneration and time course of appearance of parasite DNA in urine were not clearly different from the 12 degrees C group. These findings indicate that higher mortality at 18 degrees C compared to 12 degrees C is associated with an enhanced severity of renal pathology and increased parasite numbers.

Complex interaction between proliferative kidney disease, water temperature and concurrent nematode infection in brown trout

Proliferative kidney disease (PKD) is a temperature-dependent disease caused by the myxozoan Tetracapsuloides bryosalmonae. It is an emerging threat to wild brown trout Salmo trutta fario populations in Switzerland. Here we examined (1) how PKD prevalence and pathology in young-of-the-year (YOY) brown trout relate to water temperature, (2) whether wild brown trout can completely recover from T. bryosalmonae-induced renal lesions and eliminate T. bryo - salmonae over the winter months, and (3) whether this rate and/or extent of the recovery is influenced by concurrent infection. A longitudinal field study on a wild brown trout cohort was conducted over 16 mo. YOY and age 1+ fish were sampled from 7 different field sites with various temperature regimes, and monitored for infection with T. bryosalmonae and the nematode Raphidascaris acus. T. bryosamonae was detectable in brown trout YOY from all sampling sites, with similar renal pathology, independent of water temperature. During winter months, recovery was mainly influenced by the presence or absence of concurrent infection with R. acus larvae. While brown trout without R. acus regenerated completely, concurrently infected brown trout showed incomplete recovery, with chronic renal lesions and incomplete translocation of T. bryosalmonae from the renal interstitium into the tubular lumen. Water temperature seemed to influence complete excretion of T. bryosalmonae, with spores remaining in trout from summer-warm rivers, but absent in trout from summer-cool rivers. In the following summer months, we found PKD infections in 1+ brown trout from all investigated river sites. The pathological lesions indicated a reinfection rather than a proliferation of remaining T. bryosalmonae. However, disease prevalence in 1+ trout was lower than in YOY.

A Gly98Val mutation in the N-Myc downstream regulated gene 1 (NDRG1) in Alaskan Malamutes with polyneuropathy.

The first cases of early-onset progressive polyneuropathy appeared in the Alaskan Malamute population in Norway in the late 1970s. Affected dogs were of both sexes and were ambulatory paraparetic, progressing to non-ambulatory tetraparesis. On neurologic examination, affected dogs displayed predominantly laryngeal paresis, decreased postural reactions, decreased spinal reflexes and muscle atrophy. The disease was considered eradicated through breeding programmes but recently new cases have occurred in the Nordic countries and the USA. The N-myc downstream-regulated gene (NDRG1) is implicated in neuropathies with comparable symptoms or clinical signs both in humans and in Greyhound dogs. This gene was therefore considered a candidate gene for the polyneuropathy in Alaskan Malamutes. The coding sequence of the NDRG1 gene derived from one healthy and one affected Alaskan Malamute revealed a non-synonymous G>T mutation in exon 4 in the affected dog that causes a Gly98Val amino acid substitution. This substitution was categorized to be "probably damaging" to the protein function by PolyPhen2 (score: 1.000). Subsequently, 102 Alaskan Malamutes from the Nordic countries and the USA known to be either affected (n = 22), obligate carriers (n = 7) or healthy (n = 73) were genotyped for the SNP using TaqMan. All affected dogs had the T/T genotype, the obligate carriers had the G/T genotype and the healthy dogs had the G/G genotype except for 13 who had the G/T genotype. A protein alignment showed that residue 98 is conserved in mammals and also that the entire NDRG1 protein is highly conserved (94.7%) in mammals. We conclude that the G>T substitution is most likely the mutation that causes polyneuropathy in Alaskan Malamutes. Our characterization of a novel candidate causative mutation for polyneuropathy offers a new canine model that can provide further insight into pathobiology and therapy of human polyneuropathy. Furthermore, selection against this mutation can now be used to eliminate the disease in Alaskan Malamutes.

A comparison of estimated glomerular filtration rates using Cockcroft−Gault and the Chronic Kidney Disease Epidemiology Collaboration estimating equations in HIV infection

OBJECTIVES: The aim of this study was to determine whether the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI)- or Cockcroft-Gault (CG)-based estimated glomerular filtration rates (eGFRs) performs better in the cohort setting for predicting moderate/advanced chronic kidney disease (CKD) or end-stage renal disease (ESRD). METHODS: A total of 9521 persons in the EuroSIDA study contributed 133 873 eGFRs. Poisson regression was used to model the incidence of moderate and advanced CKD (confirmed eGFR < 60 and < 30 mL/min/1.73 m(2) , respectively) or ESRD (fatal/nonfatal) using CG and CKD-EPI eGFRs. RESULTS: Of 133 873 eGFR values, the ratio of CG to CKD-EPI was ≥ 1.1 in 22 092 (16.5%) and the difference between them (CG minus CKD-EPI) was ≥ 10 mL/min/1.73 m(2) in 20 867 (15.6%). Differences between CKD-EPI and CG were much greater when CG was not standardized for body surface area (BSA). A total of 403 persons developed moderate CKD using CG [incidence 8.9/1000 person-years of follow-up (PYFU); 95% confidence interval (CI) 8.0-9.8] and 364 using CKD-EPI (incidence 7.3/1000 PYFU; 95% CI 6.5-8.0). CG-derived eGFRs were equal to CKD-EPI-derived eGFRs at predicting ESRD (n = 36) and death (n = 565), as measured by the Akaike information criterion. CG-based moderate and advanced CKDs were associated with ESRD [adjusted incidence rate ratio (aIRR) 7.17; 95% CI 2.65-19.36 and aIRR 23.46; 95% CI 8.54-64.48, respectively], as were CKD-EPI-based moderate and advanced CKDs (aIRR 12.41; 95% CI 4.74-32.51 and aIRR 12.44; 95% CI 4.83-32.03, respectively). CONCLUSIONS: Differences between eGFRs using CG adjusted for BSA or CKD-EPI were modest. In the absence of a gold standard, the two formulae predicted clinical outcomes with equal precision and can be used to estimate GFR in HIV-positive persons.

Plasma and urine neutrophil gelatinase-associated lipocalin (NGAL) in dogs with acute kidney injury or chronic kidney disease.

BACKGROUND Neutrophil gelatinase-associated lipocalin (NGAL) is a protein that is used in human medicine as a real-time indicator of acute kidney injury (AKI). HYPOTHESIS Dogs with AKI have significantly higher plasma NGAL concentration and urine NGAL-to-creatinine ratio (UNCR) compared with healthy dogs and dogs with chronic kidney disease (CKD). ANIMALS 18 healthy control dogs, 17 dogs with CKD, and 48 dogs with AKI. METHODS Over a period of 1 year, all dogs with renal azotemia were prospectively included. Urine and plasma samples were collected during the first 24 hours after presentation or after development of renal azotemia. Plasma and urine NGAL concentrations were measured with a commercially available canine NGAL Elisa Kit (Bioporto® Diagnostic) and UNCR was calculated. A single-injection plasma inulin clearance was performed in the healthy dogs. RESULTS Median (range) NGAL plasma concentration in healthy dogs, dogs with CKD, and AKI were 10.7 ng/mL (2.5-21.2), 22.0 ng/mL (7.7-62.3), and 48.3 ng/mL (5.7-469.0), respectively. UNCR was 2 × 10(-8) (0-46), 1,424 × 10(-8) (385-18,347), and 2,366 × 10(-8) (36-994,669), respectively. Dogs with renal azotemia had significantly higher NGAL concentrations and UNCR than did healthy dogs (P < .0001 for both). Plasma NGAL concentration was significantly higher in dogs with AKI compared with dogs with CKD (P = .027). CONCLUSIONS AND CLINICAL IMPORTANCE Plasma NGAL could be helpful to differentiate AKI from CKD in dogs with renal azotemia.