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.

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.

An unusual complication of kidney biopsy: a case report.

BACKGROUND: The kidney biopsy is a routine procedure. Once an indication has been established, the benefit-risk balance may be considered. Sometimes, even with effective treatment, a severe complication may develop. CASE PRESENTATION: We present the case of a Caucasian 20-year-old young woman admitted to investigating and treating acute kidney injury. Renal involvement was characterized by kidney damage requiring hemodialysis treatment, positive immunologic testing, 0.5 g/day proteinuria, and microscopic hematuria. Contraindications were excluded, so an ultrasound-guided kidney biopsy was performed. To reduce the bleeding complication, Octostim (desmopressin) was administered. There were no direct complications following the kidney biopsy, so we continued the immunosuppressive treatment. Histologically founded thrombotic microangiopathy. However, 1 week later, severe bleeding developed with the need for urgent surgical left kidney removal. CONCLUSION: Kidney biopsy can be considered a routine procedure, and various bleeding episodes are most common in terms of complications, the detection of which is essential. Delayed bleeding complications are rare and can be caused by minor injuries. Our young patient had no injury during the hospitalization. We hypothesized that the developed serious and delayed bleeding complication resulted from effective immunosuppressive treatment. To the best of our knowledge, this is the first such case to date. However, renal biopsy in the case of thrombotic microangiopathy requires caution.

Complement-mediated dialysis reaction during regular hemodialysis treatment: a case report.

BACKGROUND: Hemodialysis reactions (HDRs) are similar to complement activation-related pseudo allergy (CARPA), a hypersensitivity reaction that occurs when administering certain (nano)drugs intravenously. The pathomechanism of CARPA was described based on animal experiments. Typical CARPA-like dialysis reactions, which occur at the start of hemodialysis, have been reported using polysulfone dialyzers. However, to our knowledge, this is the first dialysis reaction that occurred towards the end of hemodialysis treatment. CASE PRESENTATION: This report describes a 52-year-old Caucasian male patient who had been receiving chronic hemodialysis for 3 years and exhibited a CARPA reaction during his third hour of treatment. Upon activation of the microbubble alarm, the extracorporeal system recirculated for five minutes. Following reconnection, the patient exhibited a drop in systemic blood pressure, chest pain, and dyspnea after five minutes. Symptoms disappeared spontaneously after reducing the speed of the blood pump, placing the patient in a Trendelenburg position, and administering a bolus infusion from the dialysis machine. The remaining dialysis treatment was uneventful. CONCLUSION: Numerous case reports about reactions occurring with modern high-efficiency polysulfone dialyzers have been published. However, due to changes in the material structure by the manufacturers, we have not encountered such cases lately. The recently reported increase in thromboxane-B2 and pulmonary arterial pressure and complement activation upon re-infusion of extracorporeal blood following dialysis may explain the reaction observed here.

The impact of COVID-19 infection before the vaccination era on the hospitalized patients requiring hemodialysis: a single-center retrospective cohort.

Due to effective vaccinations, the COVID-19 (coronavirus disease 2019) infection that caused the pandemic has a milder clinical course. We aimed to assess the mortality of hospitalized COVID-19 patients before the vaccination era. We investigated the mortality in those patients between 1 October 2020 and 31 May 2021 who received hemodialysis treatment [patients with previously normal renal function (nCKD), patients with chronic kidney disease previously not requiring hemodialysis (CKDnonHD), chronic kidney disease (CKD), and patients on regular hemodialysis (pHD)]. In addition, participants were followed up for all-cause mortality in the National Health Service database until 1 December 2021. In our center, 83 of 108 (76.9%) were included in the analysis due to missing covariates. Over a median of 26 (interquartile range 11-266) days of follow-up, 20 of 22 (90.9%) of nCKD, 23 of 24 (95.8%) of CKDnonHD, and 17 of 37 (45.9%) pHD patients died (p < 0.001). In general, patients with nCKD had fewer comorbidities but more severe presentations. In contrast, the patients with pHD had the least severe symptoms (p < 0.001). In a model adjusted for independent predictors of all-cause mortality (C-reactive protein and serum albumin), CKDnonHD patients had increased mortality [hazard ratio (HR) 1.91, 95% confidence interval (CI), 1.02-3.60], while pHD patients had decreased mortality (HR 0.41, 95% CI 0.20-0.81) compared to nCKD patients. After further adjustment for the need for intensive care, the difference in mortality between the nCKD and pHD groups became non-significant. Despite the limitations of our study, it seems that the survival of previously hemodialysis patients was significantly better.

[Beta-thalassemia and vitamin B12 deficiency and associated complement-mediated hemolysis]. / Béta-thalassaemia, B12-vitamin-hiány és társuló komplementmediált hemolízis.

We present the case of a 67-year-old male patient admitted to our clinic due to weakness and repeated dizziness. Due to his severe microcytic anemia in his laboratory tests, he needed a transfusion of 6 units of selected blood in the days following admission. Our patient was diagnosed with beta-thalassemia minor, which was accompanied by a severe deficiency of vitamin B12. Surprisingly, parallel to vitamin B12 deficiency, we detected laboratory abnormalities indicating complement-mediated autoimmune hemolysis. After correcting the vitamin B12 deficiency, the patient's blood count improved, and the observed immunological abnormalities disappeared. Genetic testing of the hemoglobin gene confirmed the c.118C>T (p.Gln40STOP) variant in heterozygous form. Beta-thalassemia is a relatively common hematological disease, although rarely encountered in Hungary. Genetic testing of patients is possible at the Laboratory Medicine Institute of the Clinical Center in Debrecen. Unfortunately, we do not have accurate information about published domestic epidemiological data. Furthermore, establishing a diagnosis can be difficult if the disease is combined with other hematological disorders, such as the lack of vitamin B12, which can clinically mimic hemolytic anemia in certain features. Our case is considered a rarity in the literature, so in the case of a positive family history, it is recommended to screen immediate family members, which may facilitate the accurate establishment of a later diagnosis. Orv Hetil. 2023; 164(24): 954-960.

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.

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.

Hypomagnesemia as a Risk Factor and Accelerator for Vascular Aging in Diabetes Mellitus and Chronic Kidney Disease.

The age-old axiom that one is as old as his or her vessels are, calls for ongoing critical re-examination of modifiable risk factors of accelerated vascular ageing in chronic kidney diseases. Attempts to modulate vascular risk with cholesterol-lowering agents have largely failed in advanced chronic kidney disease (CKD). In addition to nitrogen waste products, many pathological biochemical processes also play a role in vascular calcification in chronic kidney damage. Magnesium, a cation vital for the body, may substantially reduce cardiovascular diseases' risk and progression. This narrative review aimed to address the relationship between hypomagnesemia and vascular calcification, which promotes further cardiovascular complications in diabetes, aging, and CKD. Articles with predefined keywords were searched for in the PubMed and Google Scholar databases with specific inclusion and exclusion criteria. We hypothesized that a decrease in serum magnesium levels contributes to increased vascular calcification and thereby increases cardiovascular mortality. In summary, based on existing evidence in the literature, it appears that simple and inexpensive oral magnesium supplementation may reduce the cardiovascular mortality of patients who are already severely affected by such diseases; in this context, the concept of 'normal' vs. 'ideal' serum magnesium levels should be carefully re-examined.

A unique case of anti-GBM disease with concomitant anti-PLA2R positivity.

BACKGROUND: Concomitant occurrence of anti-GBM disease and anti-PLA2R positive membranous nephropathy have been previously described. However, to the best of our knowledge, this is the first case report that documents the co-occurrence of the diseases proven by both serologic and histologic methods. CASE PRESENTATION: A 51-year-old woman presented to hospital with nausea, bilateral lower extremity edema, dyspnea, dark urine, and then anuria. Symptoms developed one month after an upper respiratory tract infection. Laboratory results showed acute kidney injury, and hypoalbuminemia. Immunologic examination revealed both anti-GBM and anti-PLA2R positivity. Kidney biopsy demonstrated the histological features of Goodpasture's disease and anti-PLA2R positive membranous nephropathy. Steroid, cyclophosphamide, and plasmapheresis were commenced. Despite the combined immunosuppressive, the patient remained on renal replacement therapy. CONCLUSIONS: Microbial kidney injury can trigger multiple autoimmune diseases. The simultaneous occurrence of anti-glomerular basement (anti-GBM) disease and membranous nephropathy is extremely rare. Delayed recognition leads to delayed treatment, causing worse renal and patient outcomes, as well as increased financial costs.

A porcine model of hemodialyzer reactions: roles of complement activation and rinsing back of extracorporeal blood.

Hemodialysis reactions (HDRs) resemble complement-activation-related pseudoallergy (CARPA) to certain i.v. drugs, for which pigs provide a sensitive model. On this basis, to better understand the mechanism of human HDRs, we subjected pigs to hemodialysis using polysulfone (FX CorDiax 40, Fresenius) or cellulose triacetate (SureFlux-15UX, Nipro) dialyzers, or Dialysis exchange-set without membranes, as control. Experimental endpoints included typical biomarkers of porcine CARPA; pulmonary arterial pressure (PAP), blood cell counts, plasma sC5b-9 and thromboxane-B2 levels. Hemodialysis (60 min) was followed by reinfusion of extracorporeal blood into the circulation, and finally, an intravenous bolus injection of the complement activator zymosan. The data indicated low-extent steady rise of sC5b-9 along with transient leukopenia, secondary leukocytosis and thrombocytopenia in the two dialyzer groups, consistent with moderate complement activation. Surprisingly, small changes in baseline PAP and plasma thromboxane-B2 levels during hemodialysis switched into 30%-70% sharp rises in all three groups resulting in synchronous spikes within minutes after blood reinfusion. These observations suggest limited complement activation by dialyzer membranes, on which a membrane-independent second immune stimulus was superimposed, and caused pathophysiological changes also characteristic of HDRs. Thus, the porcine CARPA model raises the hypothesis that a second "hit" on anaphylatoxin-sensitized immune cells may be a key contributor to HDRs.

Gastrointestinal symptoms as first remarkable signs of ANCA-associated granulomatosis with polyangiitis: a case report and reviews.

BACKGROUND: Systemic vasculitis associated with antineutrophil cytoplasmic autoantibodies (ANCA) have an extremely wide variety of symptoms, therefore the fast and proper diagnosis is difficult to establish even for experienced physicians. Gastrointestinal manifestations in ANCA-associated granulomatosis with polyangiitis (GPA) may be present, however, severe, life-threatening complications (such as perforations) are rare. CASE PRESENTATION: A case of an 18-year-old male patient is presented, where gastrointestinal symptoms (abdominal pain, vomiting, diarrhoea) were the first remarkable signs of GPA. The initial diagnosis of inflammatory bowel disease delayed the administration of proper immunosuppressive therapy, which might have contributed to the rare and life-threatening complication of arterial duodenal bleeding with perforation. Our systematic review of the literature found only a few case reports where gastrointestinal symptoms were the first signs of GPA, however, this entity might be more frequent if physicians would think of this possibility more often. CONCLUSIONS: Gastrointestinal bleeding is a rare but potential lethal complication of vasculitis. Consequently, we recommend investigating the patients diagnosed with GPA for gastrointestinal bleeding during the treatment.

Hypercalcemia and renal insufficiency ­ where can we start? / Hypercalcaemia és veseelégtelenség - merre induljunk?

Összefoglaló. Közleményünkben egy 63 éves férfi esetét ismertetjük, aki fáradékonyság, fogyás miatt végzett laboratóriumi vizsgálatokon igazolódó veseelégtelenség és hypercalcaemia miatt került felvételre Klinikánkra. A területen végzett röntgenvizsgálaton a koponyán frontalisan és a sacrumon csonteltérések (temporofrontalisan 13 mm-es, körülírtabb, mérsékelten intenzív árnyék és az S1-es rés sclerosisa) ábrázolódtak, ultrahangvizsgálat során lépmegnagyobbodás volt látható. Tünetei hátterében endokrin vagy malignus betegség nem igazolódott. A háttérben elsosorban myeloma multiplex merült fel, ugyanakkor azt célzott vizsgálatokkal sem megerosíteni, sem kizárni nem lehetett, így csontvelo-biopszia történt. A vesefunkció-romlás okának tisztázása végett vesebiopsziát végeztünk, melynek elozetes eredménye interstitialis nephritist véleményezett óriássejtekkel. Az angiotenzinkonvertáló enzim szérumszintjének ez okból történo vizsgálata emelkedett szintet mutatott, így esetünket Boeck-sarcoidosis extrapulmonalis manifesztációjának tartottuk. Per os szteroidkezelésre a beteg tünetei egyértelmu regressziót mutattak. A csontvelo- és vesebiopszia eredménye megerosítette a Boeck-sarcoidosis diagnózisát. A sarcoidosis ezen extrapulmonalis formája hypercalcaemiával és veseérintettséggel - de tüdoérintettség nélkül - rendkívül ritka, különös tekintettel a vesét érinto formára. Hypercalcaemia nagyjából 7,9%-ban, veseelégtelenség 1,4%-ban fordul elo. Ezen eset alapján fontos hangsúlyozni, hogy a hypercalcaemia és a veseelégtelenség hátterében a gyakoribb endokrin, malignus, hematológiai okok mellett a Boeck-sarcoidosisnak is fel kell merülnie a differenciáldiagnosztika során. Orv Hetil. 2021; 162(13): 514-518. Summary. We present the case of a 63-year-old male patient who was admitted to our Clinic with fatigue, weight loss, hypercalcemia, renal insufficiency and anemia. X-ray showed lesions on the frontal skull and sacral region. On abdominal ultrasound, splenomegaly was detected. Based on these, myeloma multiplex was the most likely initial diagnosis; this, however, could not be confirmed with targeted serum tests, therefore bone marrow biopsy was performed. To clarify the underlying cause of decreased kidney function, renal biopsy was performed, the preliminary results of which revealed interstitial nephritis accompanied by giant cells. Serum angiotensin converting enzyme level was elevated, which led to the diagnosis of Boeck sarcoidosis with extrapulmonary manifestations. Oral corticosteroid therapy was commenced that was followed by regression of the patient's symptoms and laboratory abnormalities. Both the bone marrow and the kidney biopsies supported the diagnosis of Boeck sarcoidosis. Presentation of sarcoidosis with hypercalcemia and renal insufficiency but without the involvement of the lungs is extremely rare. Hypercalcemia occurs in about 7.9% and renal insufficiency in 1.4% of the cases. Based on this case, it is important to highlight that in the background of hypercalcemia and renal failure - beside the more frequent causes such as endocrine and hematological diseases, malignancy - one is to consider the possibility of Boeck sarcoidosis as well. Orv Hetil. 2021; 162(13): 514-518.

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.

The association of overhydration with megafistulas in hemodialysis patients.

Objectives: Diffuse enlargements of arteriovenous dialysis fistulas customarily attributed to either excessive arterial inflow or central outflow stenosis. The relationship between volume status and clinically enlarged (arteriovenous) fistula (CEF) formation in end-stage renal disease (ESRD) patients is not well understood. Methods: We assessed the pre-dialysis bioimpedance spectroscopy-measured percentage of overhydration (OH%) in 13 prevalent dialysis patients with CEF development and negative angiography and compared the results with those of 52 control dialysis patients (CONTR). All patients were prevalent ESRD patients receiving thrice-weekly maintenance hemodiafiltration at an academic outpatient dialysis unit. Results: 10/13 CEF patients had OH% ≥15% as compared to 20/52 control patients (Chi square p: .02). The degree of OH% was 20.2 ± 7.4% among the CEF vs. 14.4 ± 7.1% in the control group (Student's t-test p: .01), representing 4.2 ± 3.2 vs. 2.8 ± 1.6 L of excess fluid pre-dialysis (p: .03). Patients with CEF development took an average of 1.7 ± 1.4 vs. 0.8 ± 0.8 (p: .002) antihypertensive medications compared to the CONTR patients, yet their blood pressure was higher: 156/91 vs. 141/78 mmHg (systolic/diastolic p: .03<.0001). We found no difference in fistula vintage, body mass index, age, diabetes status, or diuretic use. The odds ratio of having a CEF in patients with ≥15% OH status was 5.3 (95% CI: 1.3-21.7; p: .01), the Number Needed to Harm with overhydration was 4. Conclusions: There is an association between bioimpedance spectroscopy-measured overhydrated clinical state and the presence of CEF; either as an increased volume capacitance or as a potential cause.

Bedside placement of peritoneal dialysis catheters - a single-center experience from Hungary.

Objectives: The successful implantation of peritoneal dialysis (PD) catheters is a critical skill procedure with the potential to impact both the short- and long-term success of renal replacement therapy and the patients' survival. Methods: We retrospectively reviewed our single-center experience with nephrologist-placed minimally invasive, double-cuffed PD catheters (PDCs). Results: The recruitment period was March 2014 through December 2015. The follow-up period lasted until 2016. The mean age of the subjects was 60 ± 18 years and indications for the PD were diuretic resistant acutely decompensated chronic heart failure in seven patients (47%) and end-stage renal disease in eight (53%) patients. Comorbid conditions included diabetes (27%), ischemic heart disease (47%), advanced liver failure (27%), and a history of hypertension (73%). The cohort had a high mortality with five subjects only in severe heart failure group (33%) passing away during the index hospitalization; of the rest, two (13%) had heart transplantation, three (20%) changed modality to hemodialysis, and only five (33%) continued with maintenance PD beyond 1 month. Acute technical complications within the first month were infrequent: one catheter (6%) had drainage problems and one (6%) was lost due to extrusion. There were no serious complications (e.g., organ damage, peritonitis, etc.). Conclusions: In selected cases, particularly in severe diuretic refractory heart failure, PDC placement placed by a nephrologist is feasible with a low rate of complications even in a low-volume center setting. The catheters we placed were all functioning with only minor complications and PD could be started immediately.