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Kidney Failure: Diagnosis and Treatment of Acute and Chronic Conditions

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A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Nephrology & Urology".

Deadline for manuscript submissions: 31 August 2025 | Viewed by 16448

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Prof. Dr. Nikolina Basic-Jukic

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Department of Nephrology, Hypertension, Dialysis and Transplantation, University Hospital Center Zagreb, Zagreb, Croatia
Interests: kidney transplantation; dialysis; hemodialysis; chronic renal failure; hypertension; clinical nephrology; acute kidney injury; immunoadsorption and apheresis

Special Issue Information

Dear Colleagues,

This Special Issue is dedicated to advancing the understanding and management of kidney failure, addressing both acute and chronic conditions within the realm of clinical medicine. Our primary aim is to provide a comprehensive overview of the current research status, emphasizing the core problems faced in the diagnosis and treatment of kidney failure, as well as the different methods of renal replacement therapies and their complications. We seek to explore innovative approaches, share clinical insights, and catalyze the translation of research findings into effective medical interventions. By focusing on both acute and chronic contexts, our goal is to contribute to improved patient outcomes and enhance the overall quality of care in nephrology.

The scope of this Special Issue encompasses a broad spectrum of topics related to kidney failure, spanning from diagnostic strategies to therapeutic interventions. We invite research articles and reviews addressing issues such as biomarkers for early detection, advancements in imaging techniques, novel treatment modalities, and the integration of precision medicine. Additionally, discussions on the challenges of managing both acute and chronic kidney conditions, including complications and comorbidities, are encouraged. We aim to create a platform for interdisciplinary collaboration, bringing together clinicians, researchers, and healthcare professionals to explore holistic approaches to kidney failure care.

Prof. Dr. Nikolina Basic-Jukic
Guest Editor

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Keywords

kidney failure
renal dysfunction
hyponatremia
peritoneal dialysis
hemodialysis
renal transplantation
immunoadsorption
plasma exchange

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Research

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19 pages, 1959 KiB

Open AccessArticle

Integration of FTIR Spectroscopy and Machine Learning for Kidney Allograft Rejection: A Complementary Diagnostic Tool

by Luís Ramalhete, Rúben Araújo, Miguel Bigotte Vieira, Emanuel Vigia, Inês Aires, Aníbal Ferreira and Cecília R. C. Calado

J. Clin. Med. 2025, 14(3), 846; https://doi.org/10.3390/jcm14030846 - 27 Jan 2025

Viewed by 711

Abstract

Background: Kidney transplantation is a life-saving treatment for end-stage kidney disease, but allograft rejection remains a critical challenge, requiring accurate and timely diagnosis. The study aims to evaluate the integration of Fourier Transform Infrared (FTIR) spectroscopy and machine learning algorithms as a minimally invasive method to detect kidney allograft rejection and differentiate between T Cell-Mediated Rejection (TCMR) and Antibody-Mediated Rejection (AMR). Additionally, the goal is to discriminate these rejection types aiming to develop a reliable decision-making support tool. Methods: This retrospective study included 41 kidney transplant recipients and analyzed 81 serum samples matched to corresponding allograft biopsies. FTIR spectroscopy was applied to pre-biopsy serum samples, and Naïve Bayes classification models were developed to distinguish rejection from non-rejection and classify rejection types. Data preprocessing involved, e.g., atmospheric compensation, second derivative, and feature selection using Fast Correlation-Based Filter for spectral regions 600–1900 cm⁻¹ and 2800–3400 cm⁻¹. Model performance was assessed via area under the receiver operating characteristic curve (AUC-ROC), sensitivity, specificity, and accuracy. Results: The Naïve Bayes model achieved an AUC-ROC of 0.945 in classifying rejection versus non-rejection and AUC-ROC of 0.989 in distinguishing TCMR from AMR. Feature selection significantly improved model performance, identifying key spectral wavenumbers associated with rejection mechanisms. This approach demonstrated high sensitivity and specificity for both classification tasks. Conclusions: The integration of FTIR spectroscopy with machine learning may provide a promising, minimally invasive method for early detection and precise classification of kidney allograft rejection. Further validation in larger, more diverse populations is needed to confirm these findings’ reliability. Full article

(This article belongs to the Special Issue Kidney Failure: Diagnosis and Treatment of Acute and Chronic Conditions)

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16 pages, 2124 KiB

Open AccessArticle

Impact of Pelvic Calcification Severity on Renal Transplant Outcomes: A Prospective Single-Center Study

by Iva Žuža, Doris Dodig, Ivan Brumini, Mate Kutlić, Robert Đurić, Nataša Katalinić, Antun Gršković, Ante Jakšić, Martina Mavrinac, Tanja Ćelić, Sanjin Rački, Lidija Orlić, Jasna Nekić and Dean Markić

J. Clin. Med. 2024, 13(20), 6171; https://doi.org/10.3390/jcm13206171 - 16 Oct 2024

Viewed by 1140

Abstract

Background: Vascular calcifications (VC) are increasingly prevalent in patients with chronic kidney disease. This study aimed to assess the incidence of iliac artery calcifications in kidney transplant (KT) patients and explore the relationship between iliac VC burden measured by pelvic calcification score (PCS) and renal transplant outcomes. Methods: This prospective study involved 79 KT recipients. VC quantification, using a pre-transplant computed tomography (CT) scan, was performed by assessing calcifications in the common and external iliac arteries bilaterally, resulting in an overall PCS ranging from 0 (no calcifications) to 44 (extensive calcifications). Based on PCS values, patients were divided into three equal-sized groups: PCS Group 1 (PCS 0–4), PCS Group 2 (PCS 5–19), and PCS Group 3 (PCS > 19). Post-transplant outcomes tracked for at least 1 year were patient and graft survival, graft function (urea, creatinine, MAG-3 clearance), and incidence of MACE during the first post-transplant year. Results: Calcifications were present in at least one arterial segment in 61 patients (77.2%). One-year patient survival was 95%, and one-year graft survival was 92.4%. Patients in PCS Group 3 had significantly lower one-year patient and graft survival compared to those in PCS Group 1 and 2 (p = 0.006 and p = 0.008, respectively). MACE and renal function indicators 1-year post-transplant were similar across all PCS groups. Conclusions: Our study demonstrated that a significant majority of KT recipients exhibited iliac VC during pre-transplant CT assessments. Patients in PCS Group 3 exhibited significantly lower one-year patient and graft survival rates compared to those in PCS Groups 1 and 2, indicating that this subgroup may require more intensive post-transplant monitoring and management. Full article

(This article belongs to the Special Issue Kidney Failure: Diagnosis and Treatment of Acute and Chronic Conditions)

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14 pages, 1353 KiB

Open AccessArticle

C4d Is an Independent Predictor of the Kidney Failure in Primary IgA Nephropathy

by Nikola Zagorec, Ivica Horvatić, Dino Kasumović, Besa Osmani, Slavica Sović, Jagoda Nikić, Matija Horaček, Petar Šenjug, Krešimir Galešić and Danica Galešić Ljubanović

J. Clin. Med. 2024, 13(17), 5338; https://doi.org/10.3390/jcm13175338 - 9 Sep 2024

Viewed by 1787

Abstract

Background: C4d deposits are present in a substantial proportion of patients with IgA nephropathy (IgAN), indicating the activation of the lectin pathway (LP) of the complement system. It seems that patients with activated LP have worse renal prognosis. The aim of this study was to investigate the prevalence and prognostic significance of C4d in our cohort of patients with primary IgA nephropathy (pIgAN). Methods: Patients with pIgAN were recruited from a hospital register of kidney biopsies of the Department of Nephrology and Dialysis, Dubrava University Hospital, Zagreb. Additional immunohistochemistry staining for C4d was performed on paraffin-embedded kidney tissue, and patients were stratified into being C4d positive or C4d negative. The clinical and histologic features of patients were analyzed and compared regarding C4d positivity. The primary outcome was defined as kidney failure (KF), and predictor variables of KF and renal survival were analyzed. Results: Of a total of 95 patients with pIgAN included in the study, C4d was present in 43 (45.3%). C4d-positive patients had a higher value of systolic (p = 0.039) and diastolic (p = 0.006) blood pressure at diagnosis as well as higher 24 h proteinuria (p = 0.018), serum urate (p = 0.033), and lower eGFR (p < 0.001). C4d-positive patients had worse renal survival (p < 0.001), higher rates of disease progression to KF (p < 0.001), and higher proteinuria (p < 0.001) and lower eGFR (p < 0.001) at the last follow-up. Glomerular C4d was an independent predictor of disease progression to KF (HR = 5.87 [0.95 CI 1.06–32.44], p = 0.032). Conclusions: C4d is an independent predictor of disease progression in patients with pIgAN. C4d may be used as an additional marker of progressive disease course in IgAN. The therapeutic implications of C4d status in IgAN, particularly in terms of complement inhibitors application, are not yet known. Full article

(This article belongs to the Special Issue Kidney Failure: Diagnosis and Treatment of Acute and Chronic Conditions)

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12 pages, 475 KiB

Open AccessArticle

Immunomodulatory Effect of COVID-19 on HLA-Antibody Profile in Renal Transplant Recipients

by Marina Kljajic, Zoran Sabljic, Ivana Juric, Vesna Furic Cunko, Renata Zunec, Marija Burek Kamenaric, Bojan Jelakovic and Nikolina Basic-Jukic

J. Clin. Med. 2024, 13(8), 2383; https://doi.org/10.3390/jcm13082383 - 19 Apr 2024

Cited by 1 | Viewed by 1376

Abstract

Background/Objectives: The novel coronavirus disease 2019 (COVID-19) has led to significant morbidity and mortality among kidney transplant recipients. SARS-CoV-2 has been hypothesized to cause an unusual immunological dysregulation triggering alloimmunity and leading to graft rejection. Methods: This prospective observational cohort study assessed 321 kidney transplant recipients who had COVID-19 infection. After the infection, patients’ sera were tested for the presence of anti-HLA de novo DSA and non-DSA specificities. Logistic regression analysis and a stepwise multivariable logistic regression analysis were used to analyze the independent risk factors associated with the development of antibodies, adjusting for known confounders. The variables evaluated were acute COVID-19 characteristics (i.e., presentation, and need for hospitalization), demographic characteristics (i.e., age, gender, and primary renal disease), clinical characteristics (i.e., various comorbidities), and post-COVID-19 sequelae. Results: Anti-HLA de novo DSA developed in 18.7% of patients, while anti-HLA class I and class II non-DSA antibodies developed de novo in 84 (26.3%) and 83 (25.9%) patients, respectively. The development of DSA, HLA-DQ, and HLA-DR antibodies was predicted by the history of graft rejection. Obesity appeared to be protective against the emergence of de novo DSA. De novo DSA and HLA-DR antibody formation was positively linked with intravenous immunoglobulin use, CMV-hyperimmune globulin use, and decreased doses of immunosuppression during acute infection. Better allograft function during the acute disease was a protective factor against the formation of HLA-DQ and HLA-DR antibodies. Positive predictors of de novo DSA development were graft biopsy and the reactivation of EBV after infection. Conclusions: These findings suggest that the SARS-CoV-2 virus has an immunomodulatory effect and may be associated with an increased mortality in this population. Full article

(This article belongs to the Special Issue Kidney Failure: Diagnosis and Treatment of Acute and Chronic Conditions)

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Review

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18 pages, 328 KiB

Open AccessReview

Benefits and Pitfalls of Uraemic Toxin Measurement in Peritoneal Dialysis

by Aruni Malaweera, Louis Huang and Lawrence McMahon

J. Clin. Med. 2025, 14(4), 1395; https://doi.org/10.3390/jcm14041395 - 19 Feb 2025

Viewed by 598

Abstract

Chronic kidney disease is a global health burden with a rising incidence and prevalence in developed and developing nations. Once established, it results in a progressive accumulation of a myriad of uraemic toxins. Peritoneal dialysis (PD) uses the body’s peritoneal membrane to remove these toxins across a semipermeable membrane to restore and maintain homeostasis. Traditionally, dialysis adequacy has been measured through clearance of urea and creatinine. However, numerous studies have shown marginal links comparing the clearance of urea and creatinine with clinical outcomes reflected in the recent changes to the ISPD guidelines on dialysis adequacy. Instead, attention has focused on protein-bound uraemic toxins (PBTs). Produced by gut bacteria, these molecules are highly protein-bound and poorly removed by either dialysis or absorptive agents. Elevated concentrations of molecules such as p-cresyl sulfate and indoxyl sulfate have been associated with abnormal cellular function and poor patient outcomes. However, widespread use of these measures to determine dialysis adequacy has been limited by the need for specialized techniques required for measurement. Altering the gut microbiome to reduce generation of PBTs through increased dietary fiber might be an alternate approach to better patient outcomes, with some initial positive reports. This report explores advantages and limitations of measuring uraemic toxins in PD, now and in the foreseeable future. Full article

(This article belongs to the Special Issue Kidney Failure: Diagnosis and Treatment of Acute and Chronic Conditions)

16 pages, 268 KiB

Open AccessReview

SGLT2 Inhibitors and Their Effect on Urolithiasis: Current Evidence and Future Directions

by Živka Dika, Marijana Živko, Marina Kljajić and Bojan Jelaković

J. Clin. Med. 2024, 13(19), 6017; https://doi.org/10.3390/jcm13196017 - 9 Oct 2024

Viewed by 2257

Abstract

Urolithiasis (UL) is increasingly prevalent due to rising cardiorenometabolic diseases, posing significant management challenges despite advances in urological techniques. Sodium-glucose cotransporter-2 (SGLT2) inhibitors, primarily used for type 2 diabetes mellitus, chronic kidney disease, and heart failure, have emerged as a potential novel approach for UL treatment. These inhibitors may help reduce the risk of urolithiasis, particularly in patients with diabetes, by improving glycemic control and altering urinary chemistry, which are crucial factors in stone formation. However, the changes in urinary composition induced by SGLT2 inhibitors might also increase the risk of uric acid stone formation. This review evaluates the potential of SGLT2 inhibitors in managing UL, highlighting both the benefits and the risks. While these inhibitors show promise in reducing new and recurrent urinary stones in patients with diabetes, data on their effects in patients without diabetes who form stones are limited. Current human evidence largely comes from post hoc analyses of randomized controlled trials (RCTs) and large-scale database studies, with only one study providing detailed stone composition data. Experimental studies in animal models and cell lines have focused on calcium oxalate (CaOx) stones, showing that SGLT2 inhibitors specifically target CaOx stone formation and related renal inflammation. Although primarily studied for CaOx stones, their potential impact on other calcium-containing stones, such as calcium phosphate, remains promising. Further research is needed to explore their therapeutic potential and optimize treatment strategies. Full article

(This article belongs to the Special Issue Kidney Failure: Diagnosis and Treatment of Acute and Chronic Conditions)

18 pages, 693 KiB

Open AccessReview

Comparison of Autologous and Allogeneic Adipose-Derived Stem Cells in Kidney Transplantation: Immunological Considerations and Therapeutic Efficacy

by Ljiljana Fodor Duric, Nikolina Basic Jukic and Bozidar Vujicic

J. Clin. Med. 2024, 13(19), 5763; https://doi.org/10.3390/jcm13195763 - 27 Sep 2024

Cited by 1 | Viewed by 2208

Abstract

Regenerative medicine shows significant potential in treating kidney diseases through the application of various types of stem and progenitor cells, including mesenchymal stem cells (MSCs), renal stem/progenitor cells, embryonic stem cells (ESCs), and induced pluripotent stem cells (iPSCs). Stem cells possess the unique ability to repair injured organs and improve impaired functions, making them a key element in the research of therapies for kidney tissue repair and organ regeneration. In kidney transplantation, reperfusion injury can cause tissue destruction, leading to an initially low glomerular filtration rate and long-term impact on function by creating irreversible interstitial fibrosis. MSCs have proven useful in repairing early tissue injury in animal models of kidney, lung, heart, and intestine transplantation. The use of stem cell therapies in solid organ transplantation raises the question of whether autologous or allogeneic cells should be preferred. Adipose-derived stem cells (ASCs), characterized by the lack of HLA Class II molecules and low expression of HLA Class I and co-stimulatory signals, are considered immune-privileged. However, the actual risk of graft rejection associated with allogeneic ASCs remains unclear. It has been demonstrated that donor-derived ASCs can promote the development of Treg cells in vitro, and some degree of tolerance induction has been observed in vivo. Nevertheless, a study comparing the efficacy of autologous and allogeneic ASCs in a rat model with a total MHC mismatch for kidney transplantation showed that donor-derived administration of ASCs did not improve the grafts’ survival and was associated with increased mortality through an immunologically mediated mechanism. Given the lack of data, autologous ASCs appear to be a safer option in this research context. The aim of this review was to examine the differences between autologous and allogeneic ASCs in the context of their application in kidney transplantation therapies, considering potential immune reactions and therapeutic efficacy. Some have argued that ASCs harvested from end-stage renal disease (ESRD) patients may have lower regenerative potential due to the toxic effects of uremia, potentially limiting their use in transplantation settings. However, evidence suggests that the beneficial properties of ASCs are not affected by uremia or dialysis. Indeed, some investigators have demonstrated that ASCs harvested from chronic kidney disease (CKD) patients exhibit normal characteristics and function, maintaining consistent proliferative capacity and genetic stability over time, even after prolonged exposure to uremic serum Furthermore, no differences were observed in the response of ASCs to immune activation or their inhibitory effect on the proliferation of alloantigen-activated peripheral blood mononuclear cells between patients with normal or impaired renal function. This review presents the current achievements in stem cell research aimed at treating kidney diseases, highlighting significant progress and ongoing efforts in the development of stem cell-based therapies. Despite the encouraging results, further research is needed to overcome the current limitations and fully realize the potential of these innovative treatments. Advances in this field are crucial for developing effective therapies that can address the complex challenges associated with kidney damage and failure. Full article

(This article belongs to the Special Issue Kidney Failure: Diagnosis and Treatment of Acute and Chronic Conditions)

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10 pages, 214 KiB

Open AccessReview

JC Virus in Kidney Transplant Population: Are We Cautious Enough?

by Mirha Pjanic, Mirna Aleckovic-Halilovic and Nikolina Basic-Jukic

J. Clin. Med. 2024, 13(8), 2217; https://doi.org/10.3390/jcm13082217 - 11 Apr 2024

Viewed by 2411

Abstract

The John Cunningham virus (JCV) is a polyomavirus that usually infects people at a young age and does not cause any symptoms in immunocompetent individuals. However, in immunocompromised individuals, such as kidney transplant recipients, JCV can cause severe and potentially fatal disease. Unfortunately, JCV has not been researched as extensively as the BK virus and is not mentioned in relevant kidney transplant guidelines. This lack of attention to JCV can lead to less consideration in kidney transplant patients’ care. Surveillance using locally available diagnostic methods is of the utmost importance. The presence of JCV can be diagnosed with urine decoy cells, viruria, or viremia verified by the PCR method. A low threshold for considering JCV as a possible cause of any neurological or renal dysfunction in kidney transplant recipients must be maintained. In such cases, kidney and brain biopsy are indicated. Maintaining the appropriate immunosuppression while avoiding over-immunosuppression to prevent JCV disease is crucial, and the approach should be individual, according to overall immunological risk. We hypothesize that the presence of the JCV can indicate overt immunosuppression and identify kidney transplant recipients more prone to opportunistic infections and diseases, including some malignancies. To explore that, future observational studies are needed. Full article

(This article belongs to the Special Issue Kidney Failure: Diagnosis and Treatment of Acute and Chronic Conditions)

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9 pages, 972 KiB

Open AccessCase Report

Critically Ill Patients with Newly Diagnosed Anti-Neutrophil Cytoplasmic Antibody-Associated Vasculitis: Case Series and Literature Review

by Kresimir Rukavina, Ozrenka Zlopasa, Ivana Vukovic Brinar, Feda Dzubur, Branimir Anic and Ana Vujaklija Brajkovic

J. Clin. Med. 2024, 13(19), 5688; https://doi.org/10.3390/jcm13195688 - 25 Sep 2024

Cited by 3 | Viewed by 1248

Abstract

ANCA-associated vasculitides (AAVs) are rare diseases with a prevalence of less than 200 cases per million persons and an incidence of less than 25 cases per million person-years. Their presenting features can vary from prodromal and nonspecific symptoms to dramatic organ-specific symptoms such as respiratory failure due to diffuse alveolar hemorrhage (DAH) and acute kidney injury (AKI). The latter two are hallmark features of pulmonary-renal syndrome, a potentially fatal condition that necessitates early recognition and treatment in intensive care units (ICUs) and rapid induction of immunosuppressive therapy. Background and case summaries: We described three patients with newly diagnosed AAV during the treatment of critical illness. All patients had DAH and two had AKI. The initial disease severity was extremely high in patients with myeloperoxidase (MPO)-AAV, reaching Sequential Organ Failure Assessment (SOFA) scores of 15 and 14 with predicted mortality ≥ 95.2%. Both patients needed mechanical ventilation, one additional venovenous extracorporeal membrane oxygenation (VV-ECMO), and renal replacement therapy. The patient with proteinase 3 (PR3)-AAV had a less severe disease, SOFA 3, requiring only modest oxygen supplementation and exhibiting only hematuria with normal renal function parameters. Immunosuppressive therapy was initiated during the ICU stay. The patient with the most severe clinical presentation died during the ICU stay because of sepsis, and the other two patients were discharged home. Conclusions: Patients with AAV presenting with pulmonary-renal syndrome necessitate various degrees of organ support. Nevertheless, these patients can be successfully treated in the early, critical stages of the disease and achieve remission. Full article

(This article belongs to the Special Issue Kidney Failure: Diagnosis and Treatment of Acute and Chronic Conditions)

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10 pages, 772 KiB

Open AccessCase Report

Renal Replacement Therapy in Methylmalonic Aciduria-Related Metabolic Failure: Case Report and Literature Review

by Giovanni Pintus, Nicola Vitturi, Gianni Carraro, Livia Lenzini, Giorgia Gugelmo, Ilaria Fasan, Alberto Madinelli, Alberto Burlina, Angelo Avogaro and Lorenzo Arcangelo Calò

J. Clin. Med. 2024, 13(15), 4304; https://doi.org/10.3390/jcm13154304 - 23 Jul 2024

Cited by 1 | Viewed by 1612

Abstract

Background: Methylmalonic Aciduria (MA) without homocystinuria (or isolated MA) is a group of rare inherited metabolic disorders which leads to the accumulation of methylmalonic acid (MMA), a toxic molecule that accumulates in blood, urine, and cerebrospinal fluid, causing acute and chronic complications including metabolic crises, acute kidney injury (AKI), and chronic kidney disease (CKD). Detailed Case Description: Herein, we report a case of a 39-year-old male with MA and stage IV CKD who experienced acute metabolic decompensation secondary to gastrointestinal infection. The patient underwent a single hemodialysis (HD) session to correct severe metabolic acidosis unresponsive to medical therapy and to rapidly remove MMA. The HD session resulted in prompt clinical improvement and shortening of hospitalization. Discussion: MMA accumulation in MA patients causes acute and life-threatening complications, such as metabolic decompensations, and long-term complications such as CKD, eventually leading to renal replacement therapy (RRT). Data reported in the literature show that, overall, all dialytic treatments (intermittent HD, continuous HD, peritoneal dialysis) are effective in MMA removal. HD, in particular, can be useful in the emergency setting to control metabolic crises, even with GFR > 15 mL/min. Kidney and/or liver transplantations are often needed in MA patients. While a solitary transplanted kidney can be rapidly affected by MMA exposure, with a decline in renal function even in the first year of follow-up, the combined liver–kidney transplantation showed better long-term results due to a combination of reduced MMA production along with increased urinary excretion. Conclusions: Early diagnosis, multidisciplinary management and preventive measures are pivotal in MA patients to avoid recurrent AKI episodes and, consequently, to slow down CKD progression. Full article

(This article belongs to the Special Issue Kidney Failure: Diagnosis and Treatment of Acute and Chronic Conditions)

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