Pulmonary hypertension in patients with chronic kidney disease on dialysis and without dialysis: results of the PEPPER-study

Pulmonary hypertension (PH) is common in patients with dialysis-dependent chronic kidney disease and is an independent predictor of mortality. However, specific hemodynamics of the pulmonary circulation, changes induced by hemodialysis and characterization into pre- or postcapillary PH have not been evaluated in patients with chronic kidney disease. We assessed consecutive patients with end-stage chronic kidney disease in WHO FC ≥ II with dyspnea unexplained by other causes on hemodialysis (group 1, n = 31) or without dialysis (group 2, n = 31) using right heart catheterization (RHC). In group 1, RHC was performed before and after dialysis. In end-stage chronic kidney disease, prevalence of precapillary PH was 13% (4/31), and postcapillary PH was discovered in 65% (20/31). All four cases of precapillary PH were unmasked after dialysis. In group 2, two cases of precapillary PH were detected (6%), and postcapillary PH was diagnosed in 22 cases (71%). This is the first study examining a large cohort of patients with chronic kidney disease invasively by RHC for the prevalence of PH. The prevalence of precapillary PH was 13% in patients with end-stage kidney disease. That suggests careful screening for precapillary PH in this selected patient population. RHC should be performed after hemodialysis.     

Renal cystic disease in tuberous sclerosis: role of the polycystic kidney disease 1 gene.

Tuberous sclerosis is an autosomal dominant trait characterized by the development of hamartomatous growths in many organs. Renal cysts are also a frequent manifestation. Major genes for tuberous sclerosis and autosomal dominant polycystic kidney disease, TSC2 and PKD1, respectively, lie adjacent to each other at chromosome 16p13.3, suggesting a role for PKD1 in the etiology of renal cystic disease in tuberous sclerosis. We studied 27 unrelated patients with tuberous sclerosis and renal cystic disease. Clinical histories and radiographic features were reviewed, and renal function was assessed. We sought mutations at the TSC2 and PKD1 loci, using pulsed field- and conventional-gel electrophoresis and FISH. Twenty-two patients had contiguous deletions of TSC2 and PKD1. In 17 patients with constitutional deletions, cystic disease was severe, with early renal insufficiency. One patient with deletion of TSC2 and of only the 3' UTR of PKD1 had few cysts. Four patients were somatic mosaics; the severity of their cystic disease varied considerably. Mosaicism and mild cystic disease also were demonstrated in parents of 3 of the constitutionally deleted patients. Five patients without contiguous deletions had relatively mild cystic disease, 3 of whom had gross rearrangements of TSC2 and 2 in whom no mutation was identified. Significant renal cystic disease in tuberous sclerosis usually reflects mutational involvement of the PKD1 gene, and mosaicism for large deletions of TSC2 and PKD1 is a frequent phenomenon.     

Aluminium sucrose biscuit fillings to control hyperphosphataemia in patients undergoing dialysis.

Aluminium hydroxide is used to prevent hyperphosphataemia in patients undergoing dialysis, but many standard preparations are unpalatable. In this study hydrated aluminium sucrose was suspended in synthetic cream and used as a biscuit filling. Six patients undergoing dialysis took part in five five-week study periods comparing different forms of treatment. No significant difference was found between serum phosphate concentrations measured during standard treatment and those measured during treatment with aluminium sucrose biscuits. There was no significant difference in serum phosphate concentrations when the patients were given placebo biscuits and when they received no treatment. Aluminium sucrose presented in this form was an adequate phosphate binder and was acceptable to the patients.     

COVID-19 in patients undergoing long-term dialysis in Ontario

BACKGROUND:Patients undergoing long-term dialysis may be at higher risk of infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and of associated disease and mortality. We aimed to describe the incidence, risk factors and outcomes for infection in these patients in Ontario, Canada.METHODS:We used linked data sets to compare disease characteristics and mortality between patients receiving long-term dialysis in Ontario who were diagnosed SARS-CoV-2 positive and those who did not acquire SARS-CoV-2 infection, between Mar. 12 and Aug. 20, 2020. We collected data on SARS-CoV-2 infection prospectively. We evaluated risk factors for infection and death using multivariable logistic regression analyses.RESULTS:During the study period, 187 (1.5%) of 12 501 patients undergoing dialysis were diagnosed with SARS-CoV-2 infection. Of those with SARS-CoV-2 infection, 117 (62.6%) were admitted to hospital and the case fatality rate was 28.3%. Significant predictors of infection included in-centre hemodialysis versus home dialysis (odds ratio [OR] 2.54, 95% confidence interval [CI] 1.59–4.05), living in a long-term care residence (OR 7.67, 95% CI 5.30–11.11), living in the Greater Toronto Area (OR 3.27, 95% CI 2.21–4.80), Black ethnicity (OR 3.05, 95% CI 1.95–4.77), Indian subcontinent ethnicity (OR 1.70, 95% CI 1.02–2.81), other non-White ethnicities (OR 2.03, 95% CI 1.38–2.97) and lower income quintiles (OR 1.82, 95% CI 1.15–2.89).INTERPRETATION:Patients undergoing long-term dialysis are at increased risk of SARS-CoV-2 infection and death from coronavirus disease 2019. Special attention should be paid to addressing risk factors for infection, and these patients should be prioritized for vaccination.

As of Aug. 20, 2020, in Ontario, Canada’s most populous province, almost 41 000 people had tested positive for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the virus that causes coronavirus disease 2019 (COVID-19),¹ which represented 0.3% of the provincial population. Close to 2800 people had died, a case fatality rate of 6.8%.²Patients undergoing dialysis have high rates of comorbid conditions, are often older adults, have varying degrees of immunosuppression and are more likely to reside in long-term care, which puts them at risk of both acquiring SARS-CoV-2 and developing complicated disease.^3,4 Furthermore, in Ontario, those who receive in-centre hemodialysis typically have 3 treatments per week in outpatient units located in or affiliated with hospitals, and the consequent inability to fully self-isolate means that patients undergoing hemodialysis likely have an even higher risk of SARS-CoV-2 infection.^3,4 Recent studies support this but do not compare infection rates with those in the local population of patients not undergoing dialysis.^5–10 Several studies have reported SARS-CoV-2 infection in single or multicentre cohorts of patients undergoing dialysis,^5–10 but we are unaware of any that have identified risk factors for infection at the level of a large region. Some studies have found that patients with SARS-CoV-2 infection who are undergoing dialysis are at high risk of severe illness and death.^6–10     

Cellular pathophysiology of cystic kidney disease: insight into future therapies.

Polycystic kidney disease (PKD) is a developmental kidney disorder which can be inherited as either an autosomal dominant trait, with an incidence of 1:50 to 1:1000, or as an autosomal recessive trait with an incidence of 1:6,000 to 1:40,000. Three different genes have now been cloned that are associated with mutations that cause PKD. Two of these are linked to the most common forms of the dominant disease while the third is associated with the orpk mouse model of recessive polycystic kidney disease. Advances in understanding the molecular genetics of PKD have been paralleled by new insights into the cellular pathophysiology of cyst formation and progressive enlargement. Current data suggest that a number of PKD proteins may interact in a complex, which when disrupted by mutations in PKD genes may lead to altered epithelial proliferative activity, secretion, and cell matrix biology. The identification of a unique cystic epithelial phenotype presents new opportunities for targeted therapies. These include targeted gene therapy, gene complementation, and specific immunological or pharmacological interruption of growth factor pathways.     

The importance of body composition and dry weight assessments in patients with chronic kidney disease

Chronic volume overload is the major cause of hypertension and other cardiovascular morbidity in dialysis patients. One of the most important goals of physicians who take care of patients with chronic renal failure is to obtain near euvolemia or "dry body weight" in order to maintain or normalize blood pressure and prevent further cardiovascular events. In clinical practice, exact estimation of dry weight in hemodialysis patients remains a major challenge. Alterations in body composition, particularly malnutrition, are common in patients receiving long-term hemodialysis and contribute to a high mortality rate. In contrast, obesity - a known risk factor for cardiovascular morbidity and mortality - is prevalent amongst kidney allograft recipients in - long term after renal transplantation. Several technological tools and biochemical markers for estimation of plasma volume and body composition are available for clinical use. Our aim was to highlight the importance of control of body fluid volume and body composition in patients with chronic kidney disease and to describe the different methods available for such measurements.     

Hair trace elements in kidney dialysis patients by INAA

INAA was used to determine selected trace elements—Ca, Al, P, and S—in 104 cleaned scalp hair samples from kidney dialysis patients (n=54) and healthy controls (n=50) in order to explore any differences in these elements that might be related to prolonged dialysis and/or associated medication in comparison with blood serum levels of Al and P measured in the same clinic at the time of hair sampling. After correction for P (and Si) interference in Al content, it was observed that there were no significant differences (at 95% confidence level) in hair Al and Ca, which had been expected, whereas while there were definite increases in P and S. Multivariant factor analysis applied to the same data set, however, showed some multiple correlations among four variables: serum Al, duration of dialysis, medication, and hair Al.     

Blink reflex in end-stage-renal disease patients undergoing hemodialysis.

This study analyses the blink reflex in 20 adult male patients with terminal chronic renal failure undergoing hemodialysis. Abnormalities were found in ten patients (50%), eight of them with conduction studies showing axonal peripheral neuropathy. Dialysis time was longer for patients with blink reflex alterations (median 55.1 months) than for patients with normal blink reflex (median 36.3 months). Different types of early R1 and late R2 component abnormalities were recorded. The late response abnormalities may indicate subclinical functional or anatomical impairment of the low brainstem reticular formation in patients with chronic renal failure.     

Risk factors for sleep disorders in patients undergoing peritoneal dialysis

Sleep and Biological Rhythms - Sleep disorders in patients with end-stage renal disease are common but have rarely been reported in previous studies. Therefore, we examined the prevalence of sleep...     

Deletion of IFT20 in the mouse kidney causes misorientation of the mitotic spindle and cystic kidney disease

Primary cilia project from the surface of most vertebrate cells and are thought to be sensory organelles. Defects in primary cilia lead to cystic kidney disease, although the ciliary mechanisms that promote and maintain normal renal function remain incompletely understood. In this work, we generated a floxed allele of the ciliary assembly gene Ift20. Deleting this gene specifically in kidney collecting duct cells prevents cilia formation and promotes rapid postnatal cystic expansion of the kidney. Dividing collecting duct cells in early stages of cyst formation fail to properly orient their mitotic spindles along the tubule, whereas nondividing cells improperly position their centrosomes. At later stages, cells lacking cilia have increased canonical Wnt signaling and increased rates of proliferation. Thus, IFT20 functions to couple extracellular events to cell proliferation and differentiation.     

Alteration of energy production by the heart in CRF patients undergoing peritoneal dialysis

Cardiovascular disease is commonly observed in patients with chronic renal failure and this is a leading cause of death in patients with end-stage renal disease undergoing maintenance dialysis. Myocardial energy production is a very crucial aspect of cardiac function. Therefore, to evaluate energy metabolism of myocardial muscle in peritoneal dialysis (PD) patients, we carried out the following study using Magnetic resonance spectroscopy (MRS).Fourteen chronic renal failure patients and eight healthy volunteers were enrolled. The ratio of the phosphocreatine peak to the beta-phosphate to ATP peak (PCr/-ATP) was calculated from their MR spectra obtained by ³¹P-MR spectroscopy (Gyroscan S15, Philips). To determine the correlation between cardiac function and energy status, the left atrial diameter, the left ventricular (LV) end-diastolic diameter, the ejection fraction, the fraction of shortening and the LV mass index were measured by echocardiography. Peripheral blood sampling was also performed for creatinine, blood urea nitrogen, hematocrit, hemoglobin, ₂-microglobuline, intact parathyroid hormone.PCr/-ATP was significantly lower in PD (1.03 ± 0.15 vs. 1.40 ± 0.18: p = 0.0002), although all patients showed normal systolic function. No correlation was found between PCr/-ATP and cardiac function or hematological or biochemical markers. A negative correlation was present between PCr/-ATP and dialysis duration (r = 0.57, p < 0.05).Altered energy status of the myocardium in PD should be considered even if the patients did not show any systolic dysfunction. ³¹P-MRS is a useful tool to evaluate the energy status of the myocardium.     

Clinical and electrophysiologic findings in dialysis patients

The aim of this study was to quantitatively determine the electrophysiologic changes occurring in the peripheral nerves and muscles in patients with chronic renal failure (CRF) treated with haemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD), and to determine which electrophysiologic parameters are most commonly abnormal in uraemic patients. We investigated the relationship between the parameters of neurography and quantitative electromyography (QEMG) and clinical findings.The study included 42 patients with CRF (30 on HD and 12 on CAPD). Nerve conduction studies (NCSs) of the median, ulnar, tibial, peroneal, and sural nerves, and QEMG of the tibialis anterior and biceps brachii muscles were performed.We found axonal and/or demyelinating polyneuropathies in 97.6% of the patients (100% of HD and 91.7% of CAPD patients), but were not able to verify any significant differences between the HD and CAPD patients using NCS or QEMG. Median, ulnar, sural sensory nerve action potential (SNAP) amplitudes, peroneal CV and F-latency were the most common abnormal parameters in sensory and motor NCSs, respectively. The clinical findings only correlated with the parameters of neurography, and not with the parameters of QEMG. Sural SNAP amplitudes, peroneal and tibial CVs, F-latencies also correlated with the severity of the clinical findings in these patients, suggesting that these parameters can be used in follow up studies in these patients.In this study, most of the uraemic patients were found to have already mild or moderate neuropathies in which the objective clinical signs might be absent, even if they have some clinical symptoms. NCS showed abnormality indicating polyneuropathy in 24 out of 25 patients with clinical neuropathy signs and in 17 out of 17 patients with no clinical signs. Thus, in subclinical conditions NCS is useful to detect the abnormalities in peripheral nerves of the ureamic patients under chronic dialysis.     

Diagnosis, pathogenesis, and treatment prospects in cystic kidney disease

Cystic kidney diseases (CKDs) are a clinically and genetically heterogeneous group of disorders characterized by progressive fibrocystic renal and hepatobiliary changes. Recent findings have proven the cystogenic process to be compatible with cellular dedifferentiation, i. e. increased apoptosis and proliferation rates, altered protein sorting and secretory characteristics, as well as disorganization of the extracellular matrix. Compelling evidence suggests that cilia play a central pathogenic role and most cystic kidney disorders converge into a common pathogenic pathway. Recently, several promising trials have further extended our understanding of the pathophysiology of CKD and may have the potential for rational personalized therapies in future years. This review aims to summarize the current state of knowledge of the structure and function of proteins underlying polycystic kidney disease, to explore the clinical consequences of changes in respective genes, and to discuss potential therapeutic approaches.     

Acquired cystic kidney disease —a possible pitfall in genetic counseling

Summary A case of a 24-year-old pregnant woman on dialysis who asked for genetic counseling is reported. Differentiation between nonheritable acquired cystic kidneys and autosomal dominant polycystic kidney disease without noninvasive diagnostic procedures was nearly impossible in the reported woman. The communication underlines the problem and gives diagnostic criteria.