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Management of the Progression and Complications of CKD

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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: closed (15 December 2021) | Viewed by 40028

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Special Issue Editor

Prof. Dr. Francesco Locatelli

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Guest Editor

Department of Nephrology and Dialysis, Alessando Manzoni Hospital, Lecco, Italy
Interests: CKD; proteinuria; hypertension; anemia; ESAS; iron
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Chronic kidney disease (CKD) progression results in a worldwide clinical and economic burden for patients and society and, thus, its prevention and treatment are of paramount importance.

Proteinuria and elevated blood pressure (BP) are the most significant risk factors determining the progression CKD, and their treatment is crucial in CKD management. While it is well accepted that a stricter blood pressure control (≤130/80 mmHg) is indicated in patients with proteinuria, the exact degree of blood pressure reduction in CKD non-proteinuric patients is still under debate (<140/90 mm Hg?). The blockers of the renin–angiotensin system (RAS) are recommended as first line treatment in all CKD hypertensive patients, however, their nephroprotective efficacy is less relevant in non-proteinuric patients. Given that RAS blockers can cause acute derangements in kidney function and hyperkalemia, caution is needed regarding their use, especially in frail old nephroangiosclerotic patients or in the presence of advanced CKD. Dietetic–nutritional therapy (DNT) is an important component in conservative CKD management and should precede and be integrated in the pharmacological treatment. The objectives of DNT include the maintenance of an optimal nutritional status as well as the prevention and/or correction of signs, symptoms, and complications of CKD and, possibly, the delay in starting of dialysis. As part of the DNT, the modulation of protein and adequacy of caloric intake, control of cholesterol, sodium, potassium, and phosphorus intake is included. Finally, erythropoietin-stimulating agents and iron should be used for preventing severe anemia and associated symptoms.

Prof. Francesco Locatelli
Guest Editor

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Keywords

CKD
proteinuria
hypertension
anemia
ESAS
iron

Published Papers (11 papers)

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Research

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12 pages, 1045 KiB

Open AccessArticle

Protective Effects of Angiotensin Receptor Blockers on the Incidence of Dementia in Patients with Chronic Kidney Disease: A Population-Based Nationwide Study

by Yi-Hsien Chen, Yun-Yi Chen, Yu-Wei Fang and Ming-Hsien Tsai

J. Clin. Med. 2021, 10(21), 5175; https://doi.org/10.3390/jcm10215175 - 05 Nov 2021

Cited by 2 | Viewed by 1722

Abstract

Chronic kidney disease (CKD) is associated with dementia. Angiotensin receptor blockers (ARBs) have been widely used for delaying CKD progression; however, their effect on dementia prevention in patients with CKD remains unclear. We designed a retrospective cohort study to investigate the effects of ARBs on the incidence of dementia in patients with CKD. We selected 21,208 patients from the Taiwan nationwide database from 1 January 2006 to 31 December 2006. We identified ARB users (n = 17,466) and ARB non-users (n = 3742) and their medication possession ratio (MPR). The Cox proportional hazard model was used to estimate hazard ratios (HRs) for the incidence of dementia in ARB users in the CKD population. During the 11-year follow-up period, 2207 dementia events were recorded; multivariate-adjusted hazard ratios for dementia by ARB usage and ARB usage per MPR were 0.578 (95% CI: 0.52–0.643) and 0.996 (95% CI: 0.995–0.998), respectively. This association was observed in almost all subgroups. Dose frequency effect of ARBs was noted; patients with higher MPRs of ARBs generally had higher protection from dementia. Patients with hypertension and CKD who received ARBs had a decreased risk of dementia. Protective effects of ARBs on dementia increased with the frequency of ARB use. Full article

(This article belongs to the Special Issue Management of the Progression and Complications of CKD)

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10 pages, 292 KiB

Open AccessArticle

Novel Iron Parameters in Patients with Type 2 Diabetes Mellitus in Relation to Kidney Function

by Agnieszka Zapora-Kurel, Łukasz Kuźma, Magdalena Zakrzewska, Marcin Żórawski, Sławomir Dobrzycki, Małgorzata Twardowska-Kawalec and Jolanta Małyszko

J. Clin. Med. 2021, 10(16), 3732; https://doi.org/10.3390/jcm10163732 - 22 Aug 2021

Cited by 2 | Viewed by 2507

Abstract

Background/aims: Anemia of chronic disease is a common feature in diabetes and chronic kidney disease. Hepcidin is the key element involved in iron metabolism; however, studies on new indices of iron status are still ongoing. The aim of the study was to assess novel iron parameters in patients with type 2 diabetes mellitus in relation to kidney function. Methods: The study included 80 type 2 diabetic patients and 23 healthy volunteers. Standard laboratory measurements were used to measure the iron status, complete blood count, creatinine, the estimated glomerular filtration rate (eGFR), serum lipids, and brain natriuretic peptides (BNPs). Commercially available kits were used to measure hepcidin-25, the soluble transferrin receptor (sTfR), growth differentiation factor-15 (GDF-15), and hypoxia-inducible factor-1 alpha. Results: Anemia was present in 65% of the studied patients. The control group was found to have significantly higher hepcidin, sTfR, and GDF-15, and lower hemoglobin and iron. When compared with patients with eGFR values ≥60 mL/min/1.73 m² and <60 mL/min/1.73 m², we found that patients with higher eGFR had higher hemoglobin, ferritin, and HIF-1 alpha, lower BNP, and were younger. We found that levels of HIF-1 alpha are negligible in the studied population and were related to age only in patients with eGFR values ≥60 mL/min/1.73 m². Conclusion: A comprehensive assessment of iron status is rarely performed. Novel biomarkers of iron metabolism are not generally related to kidney function. Whether the assessment of HIF-1 alpha would be a marker of efficient anemia therapy with HIF-prolyl hydroxylase inhibitors is still a matter for further study. Full article

(This article belongs to the Special Issue Management of the Progression and Complications of CKD)

15 pages, 669 KiB

Open AccessArticle

Static and Dynamic Prediction of Chronic Renal Disease Progression Using Longitudinal Clinical Data from Taiwan’s National Prevention Programs

by Yi-Ping Chang, Chen-Mao Liao, Li-Hsin Wang, Hsiu-Hua Hu and Chih-Ming Lin

J. Clin. Med. 2021, 10(14), 3085; https://doi.org/10.3390/jcm10143085 - 13 Jul 2021

Cited by 4 | Viewed by 1800

Abstract

Kidney diseases can cause severe morbidity, mortality, and health burden. Determining the risk factors associated with kidney damage and deterioration has become a priority for the prevention and treatment of kidney disease. This study followed 1042 chronic kidney disease (CKD) patients with Stage 3–5 kidney disease who were treated at a public veteran’s hospital through the national prevention program. A total of 12.5 years of records of clinical measurements were collected and analyzed using dynamic and static Cox hazard models to predict the progression to dialysis treatment. The results showed that the statistical significance of several variables in patients with Stage 3–5 CKD was attenuated while the dynamic model was being used. The estimated glomerular filtration rate (eGFR) and urine protein to creatinine ratio (PCR) had the powerful ability to predict the progression of CKD patients with Stage 3a and Stage 3b–5 kidney disease, whereas serum calcium was also predictive for the progression of Stages 3b–5 CKD. Because these two sub-stages of Stage 3 CKD are often associated with differences in routine measurements and the risk analysis of renal dialysis, future research can use this predictive model as a reference while similar prevention programs are implemented. Full article

(This article belongs to the Special Issue Management of the Progression and Complications of CKD)

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12 pages, 465 KiB

Open AccessArticle

Ferric Carboxymatose in Non-Hemodialysis CKD Patients: A Longitudinal Cohort Study

by Roberto Minutolo, Patrizia Berto, Maria Elena Liberti, Nicola Peruzzu, Silvio Borrelli, Antonella Netti, Carlo Garofalo, Giuseppe Conte, Luca De Nicola, Lucia Del Vecchio and Francesco Locatelli

J. Clin. Med. 2021, 10(6), 1322; https://doi.org/10.3390/jcm10061322 - 23 Mar 2021

Cited by 2 | Viewed by 2321

Abstract

No information is available on the efficacy of ferric carboxymaltose (FCM) in real-world CKD patients outside the hemodialysis setting. We prospectively followed 59 non-hemodialysis CKD patients with iron deficient anemia (IDA: hemoglobin <12.0/<13.5 g/dL in women/men and TSAT < 20% and/or ferritin < 100 ng/mL) who were intolerant or non-responders to oral iron. Patients received ferric carboxymaltose (FCM) (single dose of 500 mg) followed by additional doses if iron deficiency persisted. We evaluated efficacy of FCM in terms of increase of hemoglobin, ferritin, and TSAT levels. Direct and indirect costs of FCM were also analyzed in comparison with a hypothetical scenario where same amount of iron as ferric gluconate (FG) was administered intravenously. During the 24 weeks of study, 847 ± 428 mg of FCM per patient were administered. IDA improved after four weeks of FCM and remained stable thereafter. At week-24, mean change (95%CI) from baseline of hemoglobin, ferritin and TSAT were +1.16 g/dL (0.55–1.77), +104 ng/mL (40–168) and +9.5% (5.8–13.2), respectively. These changes were independent from ESA use and clinical setting (non-dialysis CKD, peritoneal dialysis and kidney transplant). Among ESA-treated patients (n = 24), ESA doses significantly decreased by 26% with treatment and stopped either temporarily or persistently in nine patients. FCM, compared to a FG-based scenario, was associated with a cost saving of 288 euros/patient/24 weeks. Saving was the same in ESA users/non-users. Therefore, in non-hemodialysis CKD patients, FCM effectively corrects IDA and allows remarkable cost savings in terms of societal, healthcare and patient perspective. Full article

(This article belongs to the Special Issue Management of the Progression and Complications of CKD)

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10 pages, 1582 KiB

Open AccessArticle

Elderly Patients in a Large Nephrology Unit: Who Are Our Old, Old-Old and Oldest-Old Patients?

by Massimo Torreggiani, Antoine Chatrenet, Antioco Fois, Maria Rita Moio, Béatrice Mazé, Jean Philippe Coindre, Romain Crochette, Mickael Sigogne, Samuel Wacrenier, Léna Lecointre, Conrad Breuer, Hafedh Fessi and Giorgina Barbara Piccoli

J. Clin. Med. 2021, 10(6), 1168; https://doi.org/10.3390/jcm10061168 - 11 Mar 2021

Cited by 8 | Viewed by 2320

Abstract

The world population is aging, and the prevalence of chronic kidney disease (CKD) is increasing. Whether this increase is also due to the methods currently being used to assess kidney function in the elderly is still a matter of discussion. We aimed to describe the actual referral pattern of CKD patients in a large nephrology unit and test whether the use of different formulae to estimate kidney function could affect the staging and the need for specialist care in the older subset of our population. In 2019, 1992 patients were referred to our center. Almost 28% of the patients were aged ≥80 and about 6% were ≥90 years old. Among the causes of kidney disease, glomerulonephritis displayed a higher prevalence in younger patients whereas hypertensive or diabetic kidney disease were more prevalent in older patients. The prevalence of referred patients in advanced CKD stages increased with age; estimated glomerular filtration rate (eGFR) decreased with age regardless of which equation was used (chronic kidney disease epidemiology collaboration (CKD-EPI), Lund–Malmö Revised (LMR), modification of diet in renal disease (MDRD), Full Age Spectrum (FAS), or Berlin Initiative Study 1 (BIS)). With CKD-EPI as a reference, MDRD and FAS underestimated the CKD stage while LMR overestimated it. The BIS showed the highest heterogeneity. Considering an eGFR threshold limit of 45 mL/min for defining “significant” CKD in patients over 65 years of age, the variability in CKD staging was 10% no matter which equation was used. Our study quantified the weight of “old” and “old-old” patients on follow-up in a large nephrology outpatient unit and suggested that with the current referral pattern, the type of formula used does not affect the need for CKD care within the context of a relatively late referral, particularly in elderly patients. Full article

(This article belongs to the Special Issue Management of the Progression and Complications of CKD)

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12 pages, 539 KiB

Open AccessArticle

Cognitive Impairment, Chronic Kidney Disease, and 1-Year Mortality in Older Patients Discharged from Acute Care Hospital

by Mirko Di Rosa, Sonia D’Alia, Francesco Guarasci, Luca Soraci, Elisa Pierpaoli, Federica Lenci, Maddalena Ricci, Graziano Onder, Stefano Volpato, Carmelinda Ruggiero, Antonio Cherubini, Andrea Corsonello and Fabrizia Lattanzio

J. Clin. Med. 2020, 9(7), 2202; https://doi.org/10.3390/jcm9072202 - 12 Jul 2020

Cited by 4 | Viewed by 2213

Abstract

The prognostic interaction between chronic kidney disease (CKD) and cognitive impairment is still to be elucidated. We investigated the potential interaction of overall cognitive impairment or defective constructional praxis and CKD in predicting 1-year mortality among 646 older patients discharged from hospital. The estimated glomerular filtration rate (eGFR) was calculated using the Berlin Initiative Study (BIS) equation. Cognitive impairment was assessed by the Mini Mental State Exam (MMSE) and defective constructional praxis was ascertained by the inherent MMSE item. The study outcome was 1-year mortality. Statistical analysis was carried out using Cox regression. After adjusting for potential confounders, the co-occurrence of eGFR <30 and overall cognitive impairment (Hazard Ratio (HR) = 3.12, 95% Confidence Interval (CI) = 1.26–7.77) and defective constructional praxis (HR = 2.50, 95% CI = 1.08–5.77) were associated with the outcome. No significant prognostic interaction of eGFR < 30 with either overall cognitive impairment (HR = 1.99, 95% CI = 0.38–10.3) or constructional apraxia (HR = 1.68, 95% CI = 0.33–8.50) was detectable, while only cognitive deficits were found significantly associated with the outcome in the interaction models (HR = 3.12, 95% CI = 1.45–6.71 for overall cognitive impairment and HR = 2.16, 95% CI = 1.05–4.45 for constructional apraxia). Overall cognitive impairment and defective constructional praxis may be associated with increased risk of 1-year mortality among older hospitalized patients with severe CKD. However, no significant prognostic interaction between CKD and cognitive impairment could be observed. Full article

(This article belongs to the Special Issue Management of the Progression and Complications of CKD)

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11 pages, 1057 KiB

Open AccessFeature PaperArticle

Prevalence of Vertebral Fractures and Their Prognostic Significance in the Survival in Patients with Chronic Kidney Disease Stages 3‒5 Not on Dialysis

by Cristina Castro-Alonso, Luis D’Marco, Jaume Pomes, Monserrat Del Amo Conill, Ana Isabel García-Diez, Pablo Molina, María Jesús Puchades, José Manuel Valdivielso, Verónica Escudero, Jordi Bover, Juan Navarro-González, Begoña Ribas, Luis Manuel Pallardo and José Luis Gorriz

J. Clin. Med. 2020, 9(5), 1604; https://doi.org/10.3390/jcm9051604 - 25 May 2020

Cited by 12 | Viewed by 3306

Abstract

Background: The prevalence of vertebral fractures (VF) and their association with clinical risk factors and outcomes are poorly documented in chronic kidney disease (CKD) cohorts. The aim of the study was to evaluate the prevalence of VF in patients with non-dialysis dependent CKD (NDD-CKD), their value in predicting mortality and its correlation with parameters of bone mineral metabolism and vascular calcification. Materials and Methods: 612 NDD 3‒5 stage CKD patients participating in the OSERCE-2 study, a prospective, multicenter, cohort study, were prospectively evaluated and categorized into two groups according to presence or absence of VF at enrollment. VF were assessed with lateral radiographs and Genant semi-quantitative method was applied. Three radiologists specialized in musculoskeletal radiology performed consensual reading of individual images obtained using a Raim DICOM Viewer and a Canon EOS 350 camera to measure with Java Image software in those who had traditional acetate X-ray. Factors related to VF were assessed by logistic regression analysis. Association between VF and death over a 3-year follow-up was assessed by Kaplan-Meier survival curves and Cox-proportional hazard models. Results: VF were detected in 110 patients (18%). Serum phosphate levels (OR 0.719, 95% CI 0.532 to 0.972, p = 0.032), ankle-brachial index < 0.9 (OR 1.694, 95% CI 1.056‒2.717, p = 0.029) and treatment with bisphosphonates (OR 5.636, 95% CI 1.876‒16.930, p = 0.002) were independently related to the presence of VF. After a median follow-up of 35 months (IQR: 17‒37 months), 62 patients (10%) died. The causes of death were cardiovascular (n = 21, 34%) and infectious (n = 11, 18%). In the crude analysis, fractured patients group had poorer survival (log-rank test, p = 0.02). After multivariate adjustment for age, MDRD, albumin, diabetes mellitus, comorbidity, Adragao Score > 3 and serum phosphate, the presence of VF (HR 1.983, 95% CI 1.009‒3.898, p = 0.047) were an independent predictor of all-cause mortality. Conclusions: In our study 18% of patients with NDD-CKD have VF. Factors associated with VF were age, low serum phosphate levels and peripheral vascular disease. The presence of VF was an independent risk factor for mortality in stages 3‒5 NDD-CKD patients. Clinical trials are needed to confirm whether this relationship is causal and reversible with treatment for osteoporosis. Full article

(This article belongs to the Special Issue Management of the Progression and Complications of CKD)

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Review

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11 pages, 288 KiB

Open AccessReview

Focus on the Possible Role of Dietary Sodium, Potassium, Phosphate, Magnesium, and Calcium on CKD Progression

by Sandro Mazzaferro, Natalia de Martini, Jorge Cannata-Andía, Mario Cozzolino, Piergiorgio Messa, Silverio Rotondi, Lida Tartaglione, Marzia Pasquali and on behalf of the ERA-EDTA CKD-MBD Working Group

J. Clin. Med. 2021, 10(5), 958; https://doi.org/10.3390/jcm10050958 - 01 Mar 2021

Cited by 10 | Viewed by 3289

Abstract

The impressive estimated number of chronic kidney disease (CKD) patients in the world justifies any possible effort at implementing preventive measures of disease progression. Renal insufficiency is associated with significant changes in the electrolyte handling and body balance of sodium, potassium, phosphate, magnesium, and calcium, all of which are biologically vital molecules. Dietary habits could contribute significantly to the optimal management of possible derangements. In this review, we examined the available evidence recommending dietary prescriptions for these five elements aiming at reducing CKD progression. Clear evidence that specific dietary prescriptions may halt or reduce CKD progression is lacking. However, some practical recommendations are possible to prescribe the best possible therapy to the individual CKD patient. Full article

(This article belongs to the Special Issue Management of the Progression and Complications of CKD)

15 pages, 2744 KiB

Open AccessReview

ESA, Iron Therapy and New Drugs: Are There New Perspectives in the Treatment of Anaemia?

by Lucia Del Vecchio and Roberto Minutolo

J. Clin. Med. 2021, 10(4), 839; https://doi.org/10.3390/jcm10040839 - 18 Feb 2021

Cited by 15 | Viewed by 5547

Abstract

Anemia is a well-known consequence of chronic kidney disease (CKD); it is mainly due to a relative insufficiency of erythropoietin synthesis by the failing kidneys. Over the years, the combination of erythropoiesis stimulating agents (ESA) and iron has become the standard of care of anemia. All ESAs effectively increase hemoglobin (Hb) levels in a substantial percentage of patients. However, in the last decade, their use has been surrounded by safety issues in increased cardiovascular risk, especially when used at high doses in inflamed and hyporesponsive patients. This has led to the definition of a more cautious Hb target. Iron deficiency is very frequent in CKD patients, with a higher frequency in non-dialysis patients. Traditionally, iron supplementation is mostly used as supportive therapy for anemia control. However, the concept is growing that intravenous iron therapy per se could be beneficial in the presence of heart failure. A new class of drugs, prolyl hydroxylase domain (PHD) inhibitors (PHD inhibitors) is becoming available for the treatment of anemia in CKD patients. Theoretically, these agents have a number of advantages, the main ones being that of stimulating the synthesis of endogenous erythropoietin and increasing iron availability. The impact of their future use in clinical practice is still to be defined. Another possible strategy could be targeting serum hepcidin and its related pathways. This possibility is fascinating from the scientific point of view, but at present its development phase is still far from clinical application. Full article

(This article belongs to the Special Issue Management of the Progression and Complications of CKD)

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19 pages, 5356 KiB

Open AccessReview

Medical Nutritional Therapy for Patients with Chronic Kidney Disease not on Dialysis: The Low Protein Diet as a Medication

by Adamasco Cupisti, Maurizio Gallieni, Carla Maria Avesani, Claudia D’Alessandro, Juan Jesus Carrero and Giorgina Barbara Piccoli

J. Clin. Med. 2020, 9(11), 3644; https://doi.org/10.3390/jcm9113644 - 12 Nov 2020

Cited by 20 | Viewed by 10176

Abstract

The 2020 Kidney Disease Outcome Quality Initiative (KDOQI) Clinical Practice Guideline for Nutrition in chronic kidney disease (CKD) recommends protein restriction to patients affected by CKD in stages 3 to 5 (not on dialysis), provided that they are metabolically stable, with the goal to delay kidney failure (graded as evidence level 1A) and improve quality of life (graded as evidence level 2C). Despite these strong statements, low protein diets (LPDs) are not prescribed by many nephrologists worldwide. In this review, we challenge the view of protein restriction as an “option” in the management of patients with CKD, and defend it as a core element of care. We argue that LPDs need to be tailored and patient-centered to ensure adherence, efficacy, and safety. Nephrologists, aligned with renal dietitians, may approach the implementation of LPDs similarly to a drug prescription, considering its indications, contra-indications, mechanism of action, dosages, unwanted side effects, and special warnings. Following this framework, we discuss herein the benefits and potential harms of LPDs as a cornerstone in CKD management. Full article

(This article belongs to the Special Issue Management of the Progression and Complications of CKD)

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14 pages, 678 KiB

Open AccessReview

Nephroprotection by SGLT2 Inhibition: Back to the Future?

by Luca De Nicola, Francis B. Gabbai, Carlo Garofalo, Giuseppe Conte and Roberto Minutolo

J. Clin. Med. 2020, 9(7), 2243; https://doi.org/10.3390/jcm9072243 - 15 Jul 2020

Cited by 25 | Viewed by 3507

Abstract

The introduction of sodium/glucose cotransporter 2 inhibitors (SGLT2i) has opened new perspectives for the management of diabetic population at risk of or with chronic kidney disease (CKD). More important, recent, large real-world studies have repositioned the nephroprotective efficacy of SGLT2i emerged from randomized trials within the frame of effectiveness. Furthermore, the salutary effects of these agents may extend to the nondiabetic population according to the positive results of current studies. Nevertheless, the clear benefits of these agents on the prevention of organ damage contrast with their unexpected, limited use in clinical practice. One potential barrier is the acute decline in glomerular filtration rate (GFR) commonly observed at the beginning of treatment. This phenomenon is reminiscent of the early response to the traditional nephroprotective interventions, namely blood pressure lowering, dietary protein and salt restriction and the inhibition of the renin–angiotensin system. Under this perspective, the “check-mark” sign observed in the GFR trajectory over the first weeks of SGT2i therapy should renew interest on the very basic goal of CKD treatment, i.e., alleviate hyperfiltration in viable nephrons in order to prolong their function. Full article

(This article belongs to the Special Issue Management of the Progression and Complications of CKD)

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