Safety and efficacy of placement of tunneled hemodialysis catheter without the use of fluoroscopy.

INTRODUCTION: The implantation of acute or chronic vascular accesses for hemodialysis (HD) in end-stage kidney disease patients is a critical skill procedure for nephrologists, with an impact on short- and long-term outcomes of the modality and patient survival. Placement circumstances, however, may depend on the availability of technological support and will likely vary across the world. MATERIALS AND METHODS: We retrospectively reviewed our local experience with ultrasound-guided tunneled dialysis catheter (TDC) insertions but without access to fluoroscopic guidance. Data were available for 63 patients with TDCs placed by faculty nephrologists at the dialysis unit procedure rooms between March 2015 and February 2018. We reviewed circumstances of TDC placement, patient characteristics, and procedural outcomes. RESULTS: The mean age was 62 (± 41) years, and 46% of the patients were male. All TDC placements were technically successful and no major complications occurred. Most TDCs (52.8%) were a de novo placement. In the de novo patient group, there were 27 right-sided internal jugular vein (IJV) and 6 left-sided IJV cannulations. Blood pump flow was 284.6 (± 58) mL/min via the temporary catheter 1 month before and 316.7 (± 46) mL/min 1 month after TDC placement (p < 0.0001). The majority of catheter tips (63%) reached the right atrial placement position successfully. DISCUSSION: Technologically successful TDC placement can be performed without fluoroscopic tip guidance and result in improved access flows and dialysis efficacy when compared to temporary hemodialysis catheters.

Comprehensive genetic testing in children with a clinical diagnosis of ARPKD identifies phenocopies.

BACKGROUND: Autosomal recessive polycystic kidney disease (ARPKD) is genetically one of the least heterogeneous ciliopathies, resulting primarily from mutations of PKHD1. Nevertheless, 13-20% of patients diagnosed with ARPKD are found not to carry PKHD1 mutations by sequencing. Here, we assess whether PKHD1 copy number variations or second locus mutations explain these cases. METHODS: Thirty-six unrelated patients with the clinical diagnosis of ARPKD were screened for PKHD1 point mutations and copy number variations. Patients without biallelic mutations were re-evaluated and screened for second locus mutations targeted by the phenotype, followed, if negative, by clinical exome sequencing. RESULTS: Twenty-eight patients (78%) carried PKHD1 point mutations, three of whom on only one allele. Two of the three patients harbored in trans either a duplication of exons 33-35 or a large deletion involving exons 1-55. All eight patients without PKHD1 mutations (22%) harbored mutations in other genes (PKD1 (n = 2), HNF1B (n = 3), NPHP1, TMEM67, PKD1/TSC2). Perinatal respiratory failure, a kidney length > +4SD and early-onset hypertension increase the likelihood of PKHD1-associated ARPKD. A patient compound heterozygous for a second and a last exon truncating PKHD1 mutation (p.Gly4013Alafs*25) presented with a moderate phenotype, indicating that fibrocystin is partially functional in the absence of its C-terminal 62 amino acids. CONCLUSIONS: We found all ARPKD cases without PKHD1 point mutations to be phenocopies, and none to be explained by biallelic PKHD1 copy number variations. Screening for copy number variations is recommended in patients with a heterozygous point mutation.

Acute interstitial nephritis in T-cell leukemia in a pediatric patient.

Acute lymphoid leukemia is the most frequently occurring malignancy in childhood, but acute tubulointerstitial nephritis with associated acute renal failure as the leading manifestation of leukemia is extremely rare. Only a few pediatric cases have been described in the literature. We present a surprising case in which physical examination and initial investigation were not typical for leukemia. Ultrasound showed only modest kidney enlargement while laboratory results indicated acute renal failure. Renal biopsy indicated tubulointerstitial nephritis, and subsequent steroid treatment led to sudden clinical improvement. One month later, however, the patient returned with typical clinical features of leukemia. Re-evaluation of the original kidney biopsy block indicated T-cell acute lymphoid leukemia. The present case highlights the importance of renal biopsy.

Inhibition of TRPC6 by protein kinase C isoforms in cultured human podocytes.

Transient receptor potential canonical-6 (TRPC6) ion channels, expressed at high levels in podocytes of the filtration barrier, are recently implicated in the pathogenesis of various forms of proteinuric kidney diseases. Indeed, inherited or acquired up-regulation of TRPC6 activities are suggested to play a role in podocytopathies. Yet, we possess limited information about the regulation of TRPC6 in human podocytes. Therefore, in this study, we aimed at defining how the protein kinase C (PKC) system, one of the key intracellular signalling pathways, regulates TRPC6 function and expression. On human differentiated podocytes, we identified the molecular expressions of both TRPC6 and several PKC isoforms. We also showed that TRPC6 channels are functional since the TRPC6 activator 1-oleoyl-2-acetyl-sn-glycerol (OAG) induced Ca(2+) -influx to the cells. By assessing the regulatory roles of the PKCs, we found that inhibitors of the endogenous activities of classical and novel PKC isoforms markedly augmented TRPC6 activities. In contrast, activation of the PKC system by phorbol 12-myristate 13-acetate (PMA) exerted inhibitory actions on TRPC6 and suppressed its expression. Importantly, PMA treatment markedly down-regulated the expression levels of PKCα, PKCß, and PKCη reflecting their activation. Taken together, these results indicate that the PKC system exhibits a 'tonic' inhibition on TRPC6 activity in human podocytes suggesting that pathological conditions altering the expression and/or activation patterns of podocyte-expressed PKCs may influence TRPC6 activity and hence podocyte functions. Therefore, it is proposed that targeted manipulation of certain PKC isoforms might be beneficial in certain proteinuric kidney diseases with altered TRPC6 functions.

Magnesium Is a Vital Ion in the Body-It Is Time to Consider Its Supplementation on a Routine Basis.

The importance of maintaining proper magnesium intake and total body magnesium content in preserving human health remains underappreciated among medical professionals and laymen. This review aimed to show the importance of hypomagnesemia as a modifiable risk factor for developing disease processes. We searched the PubMed database and Google Scholar using the keywords 'magnesium', 'diabetes', 'cardiovascular disease', 'respiratory disease', 'immune system', 'inflammation', 'autoimmune disease', 'neurology', 'psychiatry', 'cognitive function', 'cancer', and 'vascular calcification'. In multiple contexts of the search terms, all reviews, animal experiments, and human observational data indicated that magnesium deficiency can lead to or contribute to developing many disease states. The conclusions of several in-depth reviews support our working hypothesis that magnesium and its supplementation are often undervalued and underutilized. Although much research has confirmed the importance of proper magnesium supply and tissue levels, simple and inexpensive magnesium supplementation has not yet been sufficiently recognized or promoted.

Management of chronic kidney disease: The current novel and forgotten therapies.

Chronic kidney disease (CKD) is a progressive and incurable condition that imposes a significant burden on an aging society. Although the exact prevalence of this disease is unknown, it is estimated to affect at least 800 million people worldwide. Patients with diabetes or hypertension are at a higher risk of developing chronic kidney damage. As the kidneys play a crucial role in vital physiological processes, damage to these organs can disrupt the balance of water and electrolytes, regulation of blood pressure, elimination of toxins, and metabolism of vitamin D. Early diagnosis is paramount to prevent potential complications. Treatment options such as dietary modifications and medications can help slow disease progression. In our narrative review, we have summarized the available therapeutic options to slow the progression of chronic kidney disease. Many new drug treatments have recently become available, offering a beacon of hope and optimism in CKD management. Nonetheless, disease prevention remains the most critical step in disease management. Given the significant impact of CKD on public health, there is a pressing need for further research. With the development of new technologies and advancements in medical knowledge, we hope to find more effective diagnostic tools and treatments for CKD patients.

The Importance of Genetic Testing in the Differential Diagnosis of Atypical TSC2-PKD1 Contiguous Gene Syndrome-Case Series.

BACKGROUND: In clinical practice, the possible diagnosis of tuberous sclerosis or polycystic kidney disease is primarily based on clinical criteria, which can later be verified by genetic testing. But in the case of TSC2/PKD1 contiguous gene syndrome (TSC2/PKD1-CGS), the renal appearance of the disease is more serious. Therefore, early genetic analysis is recommended. METHODS: Herein we present the report of four children with TSC2/PKD1-CGS, one involving the NTHL1 gene. We aim to emphasize the importance of genetic testing in this rare syndrome. RESULTS: During the follow-up of tuberous sclerosis and polycystic kidney disease patients, it is essential to reappraise the diagnosis if the clinical symptoms' appearance or onset time is unusual. Targeted genetic testing is recommended. However, early tumor formation necessitates the extension of genetic analysis. CONCLUSIONS: An appropriate evaluation of the phenotype is the cornerstone of diagnosing the rare TSC2/PKD1-CGS with the help of genetic results. In addition, malignant tumors could draw attention to an infrequent large deletion.

The Importance of the Nephrologist in the Treatment of the Diuretic-Resistant Heart Failure.

Heart failure is not only a global problem but also significantly limits the life prospects of these patients. The epidemiology and presentation of heart failure are intensively researched topics in cardiology. The risk factors leading to heart failure are well known; however, the real challenge is to provide effective treatments. A vicious cycle develops in heart failure of all etiologies, sooner or later compromising both cardiac and kidney functions simultaneously. This can explain the repeated hospital admissions due to decompensation and the significantly reduced quality of life. Moreover, diuretic-refractory heart failure represents a distinct challenge due to repeated hospital admissions and increased mortality. In our narrative review, we wanted to draw attention to nephrology treatment options for severe diuretic-resistant heart failure. The incremental value of peritoneal dialysis in severe heart failure and the feasibility of percutaneous peritoneal dialysis catheter insertion have been well known for many years. In contrast, the science and narrative of acute peritoneal dialysis in diuretic-resistant heart failure remains underrepresented. We believe that nephrologists are uniquely positioned to help these patients by providing acute peritoneal dialysis to reduce hospitalization dependency and increase their quality of life.