Kidney and Dialysis

Physical activity and exercise are core components of lifestyle modification strategies for the management of chronic kidney disease (CKD). Yet, physical activity levels have consistently remained poor across all stages of CKD. Exercise interventions, including aerobic and resistance training, and lifestyle interventions promoting physical activity, have been shown to improve a multitude of clinical endpoints and factors important to patients; however, despite the evidence, the provision of physical activity in clinical practice is still inadequate. The usefulness of any study hinges on the adequacy and clinical relevance of the outcomes and outcome measures used. Inconsistent reporting and wide disparities in outcome use across studies limit evidence synthesis to help guide clinical practice. The kidney exercise and physical activity field has been particularly prone to inconsistent outcome reporting. To ensure research is relevant and able to influence clinical practice and future research, we need to ensure the use (and reporting) of standardized, relevant outcome measures. Core outcome sets (COS) have been widely developed across many chronic conditions, yet these COS have not been tailored to physical activity and exercise in CKD. Outcomes in clinical research need to be relevant to the intervention being employed. From this perspective, we summarize the importance that standardizing outcomes and outcome measures may have in relation to physical activity and exercise interventions for people living with kidney disease. Full article

microRNAs (miRNAs) are promising biomarkers for different pathological models because of their stable and detectable characters in biofluids. Here, we collected urine samples from 5 beagle dogs on the 3th, 6th, and 12th day in an acute kidney injury (AKI) caused by gentamycin. miRNA levels were measured with high-throughput sequencing and the results were then differentially investigated. Gene Ontology (GO) and KEGG pathway analysis were performed to analyze potential target genes corresponding to the differentially expressed miRNAs (DE-miRNAs). Relationships between hub genes and DE-miRNAs were analyzed with STRING and Cytoscape. We identified 234 DE-miRNAs 3, 6, and 12 days after gentamycin treatment (p < 0.05). Top 10 up- and down-regulated candidate target genes of DE-miRNAs were predicted by overlapping TargetScan and miRanda results). GO and KEGG analyses for DE-miRNAs demonstrated that the DE-miRNAs target genes are mainly involved in kidney injury-related pathways, such as the insulin signaling pathway, oxytocin signaling pathway, and hedgehog signaling pathway. The network of miRNA-hub genes suggests that miR-452, miR-106a, and 106b participate in regulating the largest number of hub genes. We evaluated the miRNA signature via a canine model built by gentamycin-caused acute kidney injury. Our results represent a valuable resource for evaluating miRNAs as biomarkers of renal toxicity. Full article

HUPRA syndrome is a rare autosomal recessive mitochondrial disorder caused by a mutation in the SARS2 gene encoding mitochondrial seryl-tRNA synthetase (mtSerRS). It includes hyperuricemia, pulmonary hypertension, renal failure, and alkalosis. We present a case report of a boy aged 1 year 2 months with premature anemia, hyperuricemia, pulmonary hypertension, renal failure, and alkalosis and diagnosed with HUPRA syndrome. This disease is known to be progressive and fatal. A genetic test revealed a new previously undescribed heterozygous nucleotide variant in exons 14 and 1 of the SARS2 gene. The nucleotide substitution c.1295G > A (p.Arg432His) was detected in exon 14; according to the criteria of the American College of Medical Genetics (ACMG), this missense mutation is probably pathogenic. The nucleotide substitution c.227T > C (p.Leu76Pro) was detected in exon 1; according to the ACMG criteria, this missense mutation is a variant of unclear significance. We suggest that previously undescribed nucleotide substitutions in the SARS2 gene revealed in a patient with typical clinical presentation of the HUPRA syndrome should be considered as a pathogenic mutation. Full article

Kidney disease is associated with a wide variety of metabolic abnormalities that accompany the uremic state and the state of dialysis dependence. These include altered L-carnitine homeostasis, mitochondrial dysfunctions, and abnormalities in fatty acid metabolism. L-carnitine is essential for fatty acid metabolism and proper mitochondrial function. Deficiency in kidney disease and dialysis is caused by a reduction in endogenous renal synthesis, impaired fatty acid metabolism, a lower intake due to dietary restrictions, and nonselective clearance by the dialysis procedure. Free carnitine levels <40 µmol/L in dialysis patients can lead to dialysis-related complications, such as anemia that is hyporesponsive to erythropoietin therapy, intradialytic hypotension, cardiovascular disease, and skeletal muscle dysfunction manifested as muscle weakness and fatigue. L-carnitine deficiency is also seen in acute kidney injury (AKI) resulting from trauma and/or ischemia, drugs such as cisplatin, and from infections such as covid. A persistent state of L-carnitine deficiency can further damage kidneys and lead to multi-organ failure. Carnitine supplementation has been shown to be safe and effective in improving kidney disease-related complications resulting from drug-induced toxicity, trauma, ischemic injury, infection, and dialysis, by replenishing adequate carnitine levels and rebalancing carnitine homeostasis. In this review, we will examine the protective role of L-carnitine in reducing cellular oxidative damage and maintaining mitochondrial function together with the clinical evidence for its potential use in the management of kidney disease. Full article

The components of Cardiorenal Metabolic Syndrome (CRMS) include central obesity, insulin resistance, hypertension, metabolic dyslipidemia, proteinuria, and/or reduced glomerular filtration rate. Kidney biopsy is rarely performed in patients with CRMS; histopathology findings include glomerulopathy, podocytopathy, mesangial expansion and proliferation, glomerular basement thickening, global and segmental sclerosis, interstitial fibrosis and tubular atrophy, and arterial sclerosis and hyalinosis. We report a case of CRMS with slow progression during 10 years of follow-up on chronic kidney disease (CKD). The middle-aged patient had central obesity, hypertension, dyslipidemia, cardiovascular disease, type 2 diabetes mellitus, proteinuria, and CKD stage G3b-G4. Kidney biopsy, performed 3 years after the first presentation, led to the diagnosis of chronic thrombotic microangiopathy (TMA) and complement-associated glomerulopathy. This was not compatible with the medical history and the course of the disease, and previous kidney biopsy review showed metabolic nephropathy with glomerulomegaly, global and segmental glomerulosclerosis, tubular atrophy and interstitial fibrosis, arteriosclerosis, and lipid embolus in the lumen of one artery, and found neither TMA features nor C3 deposition. The reported case demonstrates the importance of an accurate and thoughtful reading and interpretation of kidney biopsy, and stresses that disregarding medical history may potentially mislead and alter the understanding of the true cause of CKD. Full article

Despite the increasing number of dialysis patients, there is still no clear consensus regarding when a permanent access device should be prepared and renal replacement treatment should be undertaken. The purpose of this study was to evaluate left ventricular diastolic function at the start of dialysis between patients in a planned or unplanned manner according to the 2016 recommendations of the American Society of Echocardiography/European Association of Cardiovascular Imaging (ASE/EACVI). We designed a single-center, cross-sectional study to use echocardiography to evaluate and compare left ventricular diastolic function at the onset of dialysis between patients in planned and unplanned groups. A total of 21 patients were included in our analysis (11 initiated dialysis in a planned manner and 10 did so in an unplanned manner). E/A and E/E′ were significantly high in the unplanned dialysis initiation group (p = 0.048 and p = 0.003, respectively). Furthermore, the number of patients with an E/E′ ratio of >14 and tricuspid regurgitation velocity of >2.8 was also significantly high in the unplanned dialysis initiation group (80% vs. 18%; p = 0.009, 40% vs. 0%; p = 0.035, respectively). According to the American Society of Echocardiography and the European Association of Cardiovascular Imaging Recommendation in 2016, the number of patients with left ventricular diastolic dysfunction was significantly high in the unplanned dialysis initiation group (80% vs. 18%; p = 0.009). The current study demonstrated that left ventricular diastolic dysfunction is more apparent in incident dialysis patients in an unplanned manner. Our findings suggest that the assessment of left ventricular diastolic function by echocardiography may be an indication of when to create a permanent access device and initiate dialysis. Full article

While pregnancy among end-stage kidney disease patients is rare, the number of females becoming pregnant has been increasing worldwide during the last decade. The frequency of conception in this patient group has been reported to be between 0.3% and 7% per year. The aim of this review is to summarize the latest guidelines and practice points for ensuring the best outcome for both the fetus and the mother. Full article

This study evaluated the clinical usefulness of an artificial intelligence-powered smartphone application in reducing the daily salt intake of patients with chronic kidney disease (CKD). This study included 35 patients with CKD who were classified into app users (i.e., 13 outpatients who used the app for 3 months and whose salt intake was evaluated before and after using the app) and app nonusers (i.e., 22 outpatients not using the application; their salt intake was similarly evaluated). The primary outcome was estimated as salt intake after 3 months of using the application and at a 6-month follow-up. Linear mixed model analysis revealed that app users had a significant decrease in estimated salt intake after 3 months (−2.12 g/day; 95% CI, −4.05 to −0.19; p = 0.03) compared with app nonusers but not after 6 months (−0.96 g/day; 95% CI, −3.13 to 1.20; p = 0.38). App users showed a significant decrease in body mass index at 3 months (−0.42 kg/m² [95% CI, −0.78 to −0.049; p = 0.03]) and 6 months (−0.65 kg/m² [95% CI, −1.06 to −0.24; p = 0.002]). The application promoted short-term reduction in salt intake. These results provide a strong rationale for future trials. Full article

Diabetic nephropathy (DN) is characterized by an increase in urinary albumin excretion, diabetic glomerular lesions, and a decline in glomerular filtration rate (GFR). We assessed the expression of phosphatase and tensin homolog (PTEN), nuclear factor kappa-β (NF-κB), matrix metalloproteinase-2 (MMP2), and microRNA-181 in healthy controls (HC), individuals with type 2 diabetes mellitus (T2DM) without nephropathy, and those with DN. Our study investigated the association between these genes, insulin resistance (IR), and eGFR to gain insight into their roles in the pathogenesis and progression of DN. Anthropometric measurements and biochemical tests were conducted on HC (N = 36), T2DM (N = 38) patients, and DN (N = 35) patients. We used real-time polymerase chain reaction (RT-PCR) for whole blood gene expression analysis and performed bioinformatics analyses, including protein–protein interaction, gene ontology, and co-expression networks. We compared our expression data with other GEO-Microarray datasets. Our study highlights the role of IR in the progression of nephropathy in T2DM via the PTEN-Akt-mTOR signalling pathway. We also observed a decreasing trend in the expression of MMP2 and PTEN and an increasing trend in the expression of NF-κB and miR-181b-5p with the progression of nephropathy to the severe stage. The dysregulated expression of MMP2, PTEN, NF-κB, and miR-181b-5p in patients with T2DM contributes to the progression of T2DM to DN by aggravating IR, inflammation, accelerating basement membrane thickening, mesangial matrix expansion, and renal fibrosis. Full article

Objectives: Dialysis patients suffer from xerostomia based on hyposalivation even in stimulated saliva testing. Therefore, the aim of this study was (i) to evaluate an optimized oral hygiene system with an oral care gel reducing oral dryness, supporting dental plaque control and reducing the number of gingivitis affected teeth; (ii) to document the efficacy in a randomized controlled trial with dental indices; and (iii) to record the individual’s oral health related quality of life. Methods: After ethical approval (EC-UWH 103/2019), 44 dialysis patients provided signed informed consent and were divided into two groups followed up for four weeks. Subjects of the verum group (A) received daily oral care gel OROFAN^® based on biopolymers with a mild antibacterial and saliva stimulating action. They were compared to the control group (B) who executed routine oral hygiene with conventional dentifrice and toothbrushes. At baseline (T0), the medical report and all dental indices (sialometry, DMF/S, plaque index, periodontal index, tongue coating and denture hygiene index) were assessed. After 2 weeks and 4 weeks, T1 and T2 dry mouth frequency and all dental indices were assessed. An Oral Health Impact Profile was documented at baseline (T0) and at the end of the study (T2). Results: Twenty-two subjects were allocated to group A and to group B. At baseline, there were no statistical differences concerning renal insufficiency (years on dialysis and complications), systemic diseases and dental background (caries experience, periodontal diseases, plaque index and number of gingivitis affected teeth). All subjects exhibited hyposalivation (<0.7–1.0 mL/min). The control group (B) showed no statistical differences from baseline (T0) to the end of the study (T2) in dry mouth parameters, in all dental plaque and inflammation indices and in their Oral Health Impact Profile. In contrast, the verum group (A) exhibited a highly significant (p < 0.001) decrease in xerostomia frequency, in the number of gingivitis affected teeth and in their plaque index. Furthermore, their Oral Health Impact Profile improved considerably (p < 0.01). Significance of Results: Terminally ill patients may gain better oral health and, consequently, an improved quality of life by rather simple oral care using long-lasting, edible anti-inflammatory oral hygiene gel and a dentist’s devotion. Full article

The increase in the number of patients with CKD starting dialysis treatment has become a major health problem in recent years. Osteoporosis is a typical feature of advanced age, which, in the dialysis population, is almost always accompanied by uremic osteodystrophy (CKD-MBD). These two factors are involved in the pathogenesis of fractures, which represent an important risk factor for the outcome of patients. The real consistency of fractures in CKD patients on kidney replacement therapy (KRT) requiring hospitalization in the Lombardy region (over 9,000,000 inhabitants) was analyzed using data from the regional administrative databases in the years 2011–2012. Among 8109 prevalent patients, 251 (45.8% women), with fractures after 1 January 2011, entered the analysis. A follow-up of two years (2011–2012) was considered to evaluate the incidence of more frequent fractures (femur, pelvis, hip, and spine) using ICD-9-CM codes. The most frequent sites of fractures were the femur (68.5%), hip and pelvis (47.4%), and vertebrae (12%). The patients on hemodialysis (HD) had more events than PD (3.3% vs. 1.4%; p = 0.03), while patients undergoing kidney transplantation (KTx) had a significantly lower percentage of fractures (0.6% vs. 3.3%; p < 0.001). Observed mortality was very high: the estimated gross mortality rate for any cause was 25.9% at 90 days and 34.7% at 180 days. Diabetes, peripheral vasculopathy, and heart failure were associated with a numerical increase in fractures, although this was not significant. Proton pump inhibitor drugs (PPI), vitamin K antagonists, and diphosphonates were more frequently associated with fracture occurrence. The average total cost of fractured patients was 11.4% higher than that of non-fractured patients. On multivariate analysis, age >65 years, female gender, PPI therapy, and cerebrovascular disease were found to be strongly associated with fractures in dialysis patients, whereas undergoing renal transplantation presented a reduced risk. Full article

Background: IgA nephropathy (IgAN) is one of the most common glomerular diseases worldwide. Approximately 25 percent of IgAN patients reach the kidney failure stage within twenty years of diagnosis. The histopathological examination of kidney biopsy is needed to confirm the diagnosis of IgAN. microRNA (miRNA) is a small RNA that plays an important role at the post-transcriptional level by downregulating mRNAs (messenger RNA). We tried to establish a miRNA-based biomarker for IgAN. Methods: We recruited 30 IgAN patients and 15 healthy controls as study participants after taking their informed written consent. A real-time PCR-based method was used for the absolute quantification of miRNAs. A logistic regression method and receiver operating characteristic analysis were performed to find the diagnostic and prognostic accuracy of miR-148b and let-7b for IgAN in histopathological MEST-C scores. Results: miR-148b and let-7b levels were higher in IgAN patients compared to the healthy controls. miR-148b was positively correlated with glomerular filtration rate (GFR) and negatively correlated with segmental glomerulosclerosis, tubular atrophy/interstitial fibrosis (T), and blood pressure (BP). The sensitivity, specificity, and area under the curve (AUC) of the receiver operating characteristic (ROC) for miR-148b against T were 0.87, 0.77, and 0.85, respectively. The threshold value of the miR-148b copy number was 8479 to differentiate the severe condition of IgAN. Conclusion: miR-148b can be used as a potential biomarker for IgAN. Full article

Peritonitis is a common and potentially serious complication of peritoneal dialysis (PD). Common organisms include Staphylococcus Aureus, enterococci, and coagulase-negative staphylococcus. However, Stenotrophomonas maltophilia (S. maltophilia) is an uncommon cause of PD-related infection. We describe a series of three cases of S. maltophilia PD infection (two cases of PD peritonitis and one case of PD exit-site infection) that were identified over a seven-week period in a single centre. The cases were treated with antibiotics (the primary antibiotic being co-trimoxazole) for a mean duration of 30 ± 7.9 days. All of the patients required PD catheter removal due to treatment failure with antibiotics. Hospital admission was required in two of the cases and one case resulted in mortality, with the cause of death directly associated with complications from S. maltophilia infection. A multi-disciplinary team using root-cause analysis did not identify a common link between our cases but highlighted possible risk factors contributing to these presentations. Given the relative rarity of S. maltophilia, evidence on its management options remains limited. In this article, we draw upon our own experiences and examine the literature available from previously published case reports and series. These reports highlight S. maltophilia as a complex and challenging organism to treat. Our experience demonstrated the importance of early PD catheter removal in S. maltophilia PD infection, as this is likely more effective than prolonged antibiotic therapy and hence a safer management option, considering the resistant nature of S. maltophilia. Full article

This study reviews the renal aspects of diuretic resistance occurring in diuretic treatment, mostly with loop diuretics of congestive heart failure. A short discussion on the different classes of diuretics, including the recently introduced sodium-glucose transporter 2 inhibitors, and their mechanism of action in the nephron is provided, followed by a summary of recent data discussing the different causes and pathophysiological mechanisms of diuretic resistance. The major cause of diuretic resistance appears to be localized within the distal tubule. Traditionally, the concept of compensatory post-diuretic sodium reabsorption (CPDSR) was considered the major cause of diuretic resistance; however, recent studies have disputed this traditional concept and demonstrated that patients with congestive heart failure are in constant sodium-avid state. Finally, the different options of therapeutic strategies, combining different classes of diuretics are summarized. Full article

Chronic kidney disease—mineral and bone disorder (CKD-MBD) is a systemic disorder that increases the risk of morbidity and mortality in dialysis patients. CKD-MBD is highly prevalent in dialysis patients, and appropriate treatment is important for improving their outcomes. Inorganic phosphate, fibroblast growth factor 23, parathyroid hormone, and calciprotein particles are markers for critical components and effectors of CKD-MBD, and higher circulating levels of these markers are linked to cardiovascular diseases. In this short review, we focus on the pathogenesis and management of CKD-MBD in CKD patients, especially those on dialysis therapy, and discuss the prospects for improving the management in CKD patients, including those on dialysis. Full article

Arterial dysfunction is major risk factor for cardiovascular complications, and arterial stiffness is an independent risk factor in end-stage renal disease patients. As the distance from the heart increases, arterial stiffness (pulse wave velocity) becomes progressively more marked. This generates a centrifugal stiffness gradient, which leads to partial, continuous local wave reflections, which in turn attenuate the transmission of pulsatile pressure into the microcirculation, thus limiting the potentially deleterious outcomes both upstream (on the heart: left-ventricular hypertrophy and coronary perfusion) and downstream (on the renal and cerebral microcirculation: reduced glomerular filtration and impaired cognitive functions). The impact of arterial aging is greater on the aorta and central capacitive arteries, and it is characterized by a loss or reversal of the physiological stiffness gradient between central and peripheral arteries. Recently, however, in contrast to observations on the aorta, several studies have shown less pronounced, absent, or even negative associations between muscular peripheral arteries and age–stiffness relationships, which may be associated with a decrease in or reversal of the stiffness gradient. These findings point to a potential benefit of assessing the muscular peripheral arteries to predict the risk of cardiovascular disease and suggest that reversal of the stiffness gradient may be an independent risk factor for all-cause mortality. Full article

(1) Background: Pain is a prevalent and debilitating symptom associated with kidney failure. However, the impact of pain on quality of life remains unclear. We aimed to identify the prevalence, severity and characteristics of people undertaking dialysis impacted by pain and explore the lived experience of pain (2) Methods: A cross-sectional survey was administered to people undertaking haemodialysis or via telephone to those undertaking peritoneal and home haemodialysis in a single tertiary centre. Open-ended questions were analysed using thematic analysis. (3) Results: Responses were received from 131 participants (response rate 66.8%). Most were undergoing haemodialysis (87.0%). Pain was present in 92% (n = 121) of patients with 62% (n = 81) reporting pain as severe to excruciating. Common sites of pain were joints, muscle cramps, headaches, fistula pain, non-specific back pain and neuropathy. The overarching theme from the thematic analysis was that pain was a “debilitating and accepted burden” (4) Conclusions: Pain is highly prevalent, severe and debilitating in those on dialysis. There is a need for health care providers to be proactive and attentive to the management of pain. More research is needed to identify effective treatment approaches to decrease pain burden and improve the quality of life in those with kidney failure. Full article