Kidney Health for Everyone Everywhere - from Prevention to Detection and Equitable Access to Care.

The global burden of chronic kidney disease (CKD) is rapidly increasing with a projection of becoming the 5th most common cause of years of life lost globally by 2040. Aggravatingly, CKD is a major cause of catastrophic health expenditure. The costs of dialysis and transplant consume up to 3% of the annual healthcare budget in high-income countries. However, the onset and progression of CKD is often preventable. In 2020, the World Kidney Day campaign highlights the importance of preventive interventions - be they primary, secondary or tertiary. This complementing article focuses on outlining and analyzing measures that can be implemented in every country to promote and advance CKD prevention. Primary prevention of kidney disease should focus on the modification of risk factors and addressing structural abnormalities of the kidney, urinary tracts, as well as the exposure to environmental risk factors and nephrotoxins. In persons with pre-existing kidney disease, secondary prevention, including blood pressure optimization and glycaemic control, should be the main goal of education and clinical interventions. In patients with advanced CKD, the management of co-morbidities such as uraemia and cardiovascular disease is a highly recommended preventive intervention to avoid or delay dialysis or kidney transplantation. Political efforts are needed to proliferate this preventive approach. While national policies and strategies for non-communicable diseases might be in place in all or every country. Also, specific policies directed toward education and awareness about CKD screening, management and treatment are often lacking. Hence, there is an urgent need to increase the awareness and importance of preventive measures among populations, professionals and policy makers.

[Kidney health for everyone everywhere - from prevention to detection and equitable access to care].

The global burden of chronic kidney disease (CKD) is rapidly increasing with a projection of becoming the 5th most common cause of years of life lost globally by 2040. Aggravatingly, CKD is a major cause of catastrophic health expenditure. The costs of dialysis and transplantation consume up to 3% of the annual healthcare budget in high-income countries. Crucially, however, the onset and progression of CKD is often preventable. In 2020, the World Kidney Day campaign highlights the importance of preventive interventions be it primary, secondary or tertiary. This complementing article focuses on outlining and analyzing measures that can beimplemented in every country to promote and advance CKD prevention. Primary prevention of kidney disease should focus on the modification of risk factors and addressing structural abnormalities of the kidney and urinary tracts, as well as exposure to environmental risk factors and nephrotoxins. In persons with pre-existing kidney disease, secondary prevention, including blood pressure optimization and glycemic control, should be the main goal of education and clinical interventions. In patients with advanced CKD, management of co-morbidities such as uremia and cardiovascular disease is a highly recommended preventative intervention to avoid or delay dialysis or kidney transplantation. Political efforts are needed to proliferate the preventive approach. While national policies and strategies for non-communicable diseases might be present in a country, specific policies directed toward education and awareness about CKD screening, management and treatment are often lacking. Hence, there is an urgent need to increase the awareness of the importance of preventive measures throughout populations, professionals and policy makers.

The contribution of genetic variants of SLC2A1 gene in T2DM and T2DM-nephropathy: association study and meta-analysis.

An association study was conducted to investigate the relation between 14 variants of glucose transporter 1 gene (SLC2A1) and the risk of type 2 diabetes (T2DM) leading to nephropathy. We also performed a meta-analysis of 11 studies investigating association between diabetic nephropathy (DN) and SLC2A1 variants. The cohort included 197 cases (T2DM with nephropathy), 155 diseased controls (T2DM without nephropathy) and 246 healthy controls. The association of variants with disease progression was tested using generalized odds ratio (ORG). The risk of type 2 diabetes leading to nephropathy was estimated by the OR of additive and co-dominant models. The mode of inheritance was assessed using the degree of dominance index (h-index). We synthesized results of 11 studies examining association between 5 SLC2A1 variants and DN. ORG was used to assess the association between variants and DN using random effects models. Significant results were derived for co-dominant model of rs12407920 [OR = 2.01 (1.17-3.45)], rs841847 [OR = 1.73 (1.17-2.56)] and rs841853 [OR = 1.74 (1.18-2.55)] and for additive model of rs3729548 [OR = 0.52 (0.29-0.90)]. The mode of inheritance for rs12407920, rs841847 and rs841853 was 'dominance of each minor allele' and for rs3729548 'non-dominance'. Frequency of one haplotype (C-G-G-A-T-C-C-T-G-T-C-C-A-G) differed significantly between cases and healthy controls [p = .014]. Regarding meta-analysis, rs841853 contributed to an increased risk of DN [(ORG = 1.43 (1.09-1.88); ORG = 1.58 (1.01-2.48)] between diseased controls versus cases and healthy controls versus cases, respectively. Further studies confirm the association of rs12407920, rs841847, rs841853, as well as rs3729548 and the risk of T2DM leading to nephropathy.

Kidney health for all: bridging the gap in kidney health education and literacy.

The high burden of kidney disease, global disparities in kidney care, and the poor outcomes of kidney failure place a growing burden on affected individuals and their families, caregivers, and the community at large. Health literacy is the degree to which individuals and organizations have, or equitably enable individuals to have, the ability to find, understand, and use information and services to make informed health-related decisions and actions for themselves and others. Rather than viewing health literacy as a patient deficit, improving health literacy lies primarily with health care providers communicating and educating effectively in codesigned partnership with those with kidney disease. For kidney policy makers, health literacy is a prerequisite for organizations to transition to a culture that places the person at the center of health care. The growing capability of and access to technology provides new opportunities to enhance education and awareness of kidney disease for all stakeholders. Advances in telecommunication, including social media platforms, can be leveraged to enhance persons' and providers' education. The World Kidney Day declares 2022 as the year of "Kidney Health for All" to promote global teamwork in advancing strategies in bridging the gap in kidney health education and literacy. Kidney organizations should work toward shifting the patient-deficit health literacy narrative to that of being the responsibility of health care providers and health policy makers. By engaging in and supporting kidney health-centered policy making, community health planning, and health literacy approaches for all, the kidney communities strive to prevent kidney diseases and enable living well with kidney disease.

Familial collapsing focal segmental glomerulosclerosis.

The majority of patients with non-HIV-related collapsing focal segmental glomerular sclerosis (FSGS) have idiopathic disease. Only a few genetic forms associated with rare syndromes have been described in families. Here we report two families with multiple members who have collapsing FSGS with no clear associated secondary etiology. Genetic analysis revealed a defect in the TRPC6 gene in one family, but excluded all known common inherited podocyte defects in the other family. The course and response to treatment differed dramatically among members of the same family.

Aeromonas hydrophila as a causative organism in peritoneal dialysis-related peritonitis: case report and review of the literature.

Most episodes of peritoneal dialysis (PD)-related peritonitis could be attributed to a single organism, but in almost 10% of peritonitis episodes multiple organisms are identified. Polymicrobial peritonitis is often related to intra-abdominal pathology, and the prognosis may be poor. Aeromonas spp. have rarely been identified as the causative pathogen in PD-related peritonitis, and a very small number of cases has been reported in the literature. These rod-shaped, gram-negative microorganisms have been isolated from wastewater drainage systems, food, vegetables, and soil. Herein we report a case of polymicrobial peritonitis in a continuous ambulatory peritoneal dialysis (CAPD) patient with systemic lupus erythematosus (SLE), due to a combination of Streptococcus viridans and Aeromonas hydrophila infection. The patient was involved in gardening and was not compliant with her technique protocol. She did not wear a mask and omitted thorough hand washing. The patient was treated with i.p. vancomycin and ceftazidime and peritonitis was resolved. The patient's technique was reassessed, and she was retrained by our PD nurses.

Kidney health for everyone everywhere - from prevention to detection and equitable access to care.

The global burden of chronic kidney disease (CKD) is rapidly increasing with a projection of becoming the 5th most common cause of years of life lost globally by 2040. CKD is a major cause of catastrophic health expenditure. The costs of dialysis and transplantation consume up to 3% of the annual healthcare budget in high-income countries. However, the onset and progression of CKD is often preventable. In 2020, the World Kidney Day campaign highlights the importance of preventive interventions - be it primary, secondary, or tertiary. This article focuses on outlining and analyzing measures that can be implemented in every country to promote and advance CKD prevention. Primary prevention of kidney disease should focus on the modification of risk factors and addressing structural abnormalities of the kidney and urinary tracts, as well as exposure to environmental risk factors and nephrotoxins. In persons with pre-existing kidney disease, secondary prevention, including blood pressure optimization and glycemic control, should be the main goal of education and clinical interventions. In patients with advanced CKD, management of co-morbidities such as uremia and cardiovascular disease is a highly recommended preventative intervention to avoid or delay dialysis or kidney transplantation. Political efforts are needed to proliferate the preventive approach. While national policies and strategies for non-communicable diseases might be present in a country, specific policies directed toward education and awareness about CKD screening, management, and treatment are often lacking. Hence, there is an urgent need to increase the awareness of preventive measures throughout populations, professionals, and policy makers.

Predictors of Outcomes of Living Kidney Donation: Impact of Sex, Age and Preexistent Hypertension.

CONTEXT: Living kidney donation is considered a safe procedure with excellent outcomes. The great demand for organs has changed the suitability criteria for donation and older or hypertensive donors are increasingly accepted. METHODS: We reviewed the charts of 200 adults who donated a kidney at the University Hospital Hannover. Data regarding diastolic, systolic, mean blood pressure, renal function, and proteinuria at baseline and post-donation follow-up visits were recorded. A Mann-Whitney U test was performed to compare the post-nephrectomy development of blood pressure, estimated glomerular filtration rate (eGFR), and proteinuria between men and women, hypertensives and normotensives, and older (≥65 years) and younger (<65 years) donors. Multivariable time-dependent Cox regression models were used to evaluate eGFR decline post-donation, after adjustment for covariates. RESULTS: The majority of donors were female (64.5%), and 29.0% had pre-existing hypertension. The mean age at donation was 49 years, and 9.5% were older than 65 years. During a median follow-up of 3 years, no significant differences in proteinuria and change in renal function were observed between both sexes or hypertensive and normotensive donors. In contrast, older donors exhibited a faster decline in renal function. Mean eGFR (chronic kidney disease epidemiology collaboration equation) pre-donation was 99.6 ± 21.9 mL/min in younger donors and 77.6 ± 17.7 mL/min in older donors (P < .001). The respective mean values at the last follow-up visit were 81.3 ± 24.0 and 46.8 ± 17.9 mL/min (P < .001). After adjustment for sex and preexisting hypertension, compared to younger donors, older donors had a 2.39 hazard ratio for eGFR decline. CONCLUSION: Older adults display a faster decline in renal function after donation and thus should be carefully evaluated for suitability before donation.

A case of membranous nephropathy associated with Sjögren syndrome, polymyositis and autoimmune hepatitis.

Sjögren syndrome (SS) is a chronic systemic autoimmune disease characterized by lymphocytic infiltration of exocrine glands, especially lacrimal and salivary. The immunologic process which occurs in this syndrome is B cell hyperactivity, which results in production of autoantibodies and immune complexes. SS can exist as a primary disorder or in association with other autoimmune processes. A usually mild, proximal and insidious inflammatory myopathy can occur in patients with SS with a broad clinical and pathological spectrum. Interstitial nephritis with mild proteinuria and tubular dysfunction is the most common renal manifestation of SS, but glomerular involvement due to immune complex deposition may also rarely occur [Goules et al. 2000]. There is an association of SS with hepatic abnormalities, as evidenced by abnormal liver biochemical tests or histological characteristics of primary biliary cirrhosis (PBC), portal tract fibrosis, or autoimmune hepatitis [Abraham et al. 2004]. The pathogenetic mechanism of liver involvement in SS is not clear, but it is possible that hepatic and salivary gland damage share a similar pathology. The combination of Sjögren syndrome with kidney, liver and muscle involvement in one entity is extremely rare and data in the literature are remarkably sparse. We present a case of a 43-year-old female patient suffering from SS accompanied by polymyositis, membranous nephropathy and autoimmune hepatitis.

Acute renal failure after antibiotic-impregnated bone cement treatment of an infected total knee arthroplasty.

Antibiotic-impregnated cement is used frequently in revision procedures of infected total hip and knee arthroplasties. Local antibiotic treatment is as effective as the use of systemic antibiotics. The purpose of such treatment is to provide high tissue concentrations of antibiotics and minimize systemic toxicity, especially nephrotoxicity. Though antibiotic-impregnated cement is considered safe in terms of nephrotoxicity, two cases that have implicated aminoglycoside-impregnated cement in acute renal failure (ARF) after surgery for an infected total knee arthroplasty (TKA) have been reported [Curtis et al. 2005, Van Raaij et al. 2002]. Two more cases of postoperative ARF after use of combined tobramycin- plus vancomycin-impregnated cement, this time in total hip arthroplasty, have been recently reported [Patrick et al. 2006]. We report a case of ARF in a 61-year-old patient with a history of diabetes mellitus and hypertension after treatment of a febrile infection of a TKA with combined gentamicin- plus vancomycin-impregnated cement. The ARF could not sufficiently be attributed to other causes and though serum concentrations of antibiotics obtained from the 8th postoperative day and thereafter were far below the trough levels associated with nephrotoxicity, gentamicin and vancomycin seem to have contributed significantly to ARF in our case.

Matrix metalloproteinase-1 and -2 as markers of mineral bone disease in chronic kidney disease patients.

BACKGROUND: In the past few years, a distinct and multifactorial clinical entity called chronic kidney disease-mineral and bone disorder (CKD-MBD) that leads to decreased bone density and osteoporosis has been identified. The aim of this study was to assess the levels of the matrix metalloproteinase-1 and -2 (MMP-1 and MMP-2) in chronic kidney disease (CKD) patients of various disease stages in correlation to other bone turnover markers (BTM). This study is an initial investigative approach to a possible role of matrix metalloproteinases (MMPs) in the evaluation of bone disease in uremic patients. METHODS: We enrolled 60 patients at different stages of pre-dialysis CKD, 20 patients on hemodialysis (HD), and 20 age-matched healthy controls. Serum intact parathyroid hormone (iPTH), osteocalcin (OC), N-terminal propeptide of type I collagen (P1NP), and beta-C-terminal telopeptide of type I collagen (ß-CTX), were measured by electrochemiluminescence on automatic analyzers. Serum MMP-1 and MMP-2 levels were estimated using a commercial enzyme-linked immunosorbent assay (ELISA). Serum levels of urea, creatinine, calcium, phosphorus, and alkaline phosphatase were estimated. Creatinine clearance (ClCr) was calculated using the traditional clearance formula based on a 24-hour urine collection. RESULTS: Serum iPTH, OC, P1NP, ß-CTX concentrations were significantly higher (p <0.0001) while ClCr was significantly lower (p <0.0001) in CKD patients, as compared with those of healthy controls. A positive correlation was established between serum MMP-1 and OC levels (r =0.245, p =0.014), as well as with serum ß-CTX levels (r =0.197, p =0.048), and a negative correlation between MMP-2 and OC (r =-0.222, p =0.025). CONCLUSIONS: In CKD patients MMP-1 serum levels may reflect increased bone turnover rates. HIPPOKRATIA 2017, 21(1): 25-31.

Kidney health for all: bridging the gap in kidney health education and literacy

The high burden of kidney disease, global disparities in kidney care, and the poor outcomes of kidney failure place a growing burden on affected individuals and their families, caregivers, and the community at large. Health literacy is the degree to which individuals and organizations have, or equitably enable individuals to have, the ability to find, understand, and use information and services to make informed health-related decisions and actions for themselves and others. Rather than viewing health literacy as a patient deficit, improving health literacy lies primarily with health care providers communicating and educating effectively in codesigned partnership with those with kidney disease. For kidney policy makers, health literacy is a prerequisite for organizations to transition to a culture that places the person at the center of health care. The growing capability of and access to technology provides new opportunities to enhance education and awareness of kidney disease for all stakeholders. Advances in telecommunication, including social media platforms, can be leveraged to enhance persons' and providers' education. The World Kidney Day declares 2022 as the year of "Kidney Health for All" to promote global teamwork in advancing strategies in bridging the gap in kidney health education and literacy. Kidney organizations should work toward shifting the patient-deficit health literacy narrative to that of being the responsibility of health care providers and health policy makers. By engaging in and supporting kidney health-centered policy making, community health planning, and health literacy approaches for all, the kidney communities strive to prevent kidney diseases and enable living well with kidney disease.

Expression of transforming growth factor-beta receptor II mRNA in cyclosporine-induced gingival overgrowth.

Gingival overgrowth (GO), characterized by increased cellular and extracellular matrix components in gingival tissue, is a frequent side effect of cyclosporine (CsA). In previous studies, elevated levels of transforming growth factor-beta (TGF-beta) have been detected in GO tissue, which led to the conclusion that TGF-beta plays a major part in the pathogenesis. TGF-beta activity is mediated by three receptors; TGF-beta receptor II (TGF-beta RII), the most important, has been immunohistochemically detected in GO and normal gingival tissue. The aim of this study was to clarify whether TGF-beta RII is overexpressed in CsA-induced GO. The expression of TGF-beta RII mRNA in GO tissue of patients on CsA (n = 10, 5 women, aged 42.5 +/- 14.9 years) with renal transplantation (transplant duration 3.6 +/- 0.96 years) was compared with that in healthy gingiva of control subjects (n = 10, 5 women, aged 42.5 +/- 7.6 years). Semiquantitative reverse transcribed-polymerase chain reactions (RT-PCR) were applied with glyceraldehyde-3-phosphate dehydrogenase (GAPDH) as an internal standard. TGF-beta RII mRNA was readily detected in the GO tissue of patients on CsA. The level of TGF-beta RII mRNA relative to GAPDH in GO cases was not significantly higher than the relative TGF-beta mRNA level in normal gingiva (0.60 +/- 0.16 vs 0.52 +/- 0.19; P = .575). The precise mechanism of CsA-induced GO remains uncertain. According to our results, TGF-beta RII was not upregulated in CsA-induced GO, and may have no important role in this disorder. However, the involvement of TGF-beta in the molecular pathology of GO may be mediated via TGF-beta RI or RIII.

Influence of hemodialysis on the mean blood flow velocity in the middle cerebral artery.

BACKGROUND: Several effects of hemodialysis, including hemoconcentration, alterations of hemostasis or hemorheology and endothelial activation, could potentially interfere with cerebral blood flow (CBF) regulation. These treatment-specific changes may also be crucial for the enhanced incidence of stroke in uremic patients. Nevertheless, the influence of hemodialysis on CBF has not been yet adequately studied. PATIENTS AND METHODS: We registered mean blood flow velocity (MFV) in the middle cerebral artery (MCA) during hemodialysis treatment in order to evaluate its contribution on CBF changes. Transcranial Doppler ultrasonography (TCD) of the MCA was performed continuously during hemodialysis treatment in 18 stable patients (10 males and 8 females, mean age 62 +/- 11 years) with end-stage renal disease of various origin. Blood pressure (mmHg), heart rate (/min), ultrafiltration volume (ml), BV changes (deltaBV by hemoglobinometry, %), arterial blood gases (pO2, blood oxygen content, pCO2), hemostasis activation (thrombin-antithrombin III complex, ELISA) and fibrinogen (Clauss) were measured simultaneously at the beginning of treatment and every hour thereafter. RESULTS: Before the hemodialysis session the MFV in the MCA was within normal range (57.5 +/- 13.0 cm/s, ref. 60 +/- 12) and was mainly dependent on the patients' age (r = -0.697, p < 0.01). The blood flow velocity in the MCA decreased significantly from 57.5 +/- 13.0 cm/s before the beginning to 48.3 +/- 11.1 cm/s after four hours (n = 18, p < 0.05) and to 43.9 +/- 8.9 cm/s after five hours (n = 9, p < 0.05) of hemodialysis treatment. During hemodialysis treatment, the percentual changes of MFV in the MCA (delta%MFV) were interrelated to the ultrafiltration volume (r = -0.486, p < 0.01), the blood volume (BV%, r = 0.369, p < 0.01) and the percentual changes of the hematocrit (r = -0.358, p < 0.01), of the arterial blood oxygen content (delta%acO2, r = -0.420, p < 0.01) and of the plasma fibrinogen levels (delta%fibrinogen, r = 0.244, p < 0.05). CONCLUSION: A significant continuous decrease of the MFV in the MCA was observed during hemodialysis treatment, which inversely correlated both with ultrafiltration volume, BV changes and changes of plasma fibrinogen. The ultrafiltration-induced hemoconcentration with concomitant rise of hematocrit and oxygen transport capacity, may partly explain the alterations in the cerebral MFV observed during hemodialysis.

Accidental acute metabolic acidosis due to inappropriate selection of bicarbonate concentrate.

Haemodialysis using a bicarbonate concentrate (bicarbonate dialysis) is the treatment modality of choice for correction of metabolic acidosis in chronic renal failure. However, improper ratios of acid and bicarbonate concentrates in dialysis fluid can result in an iatrogenically induced metabolic acidosis. The following report presents a case of acute metabolic acidosis, which resulted from the accidental use of an inappropriate bicarbonate concentrate for haemodialysis treatment. Awareness of the problem and a rapid examination of the dialysis fluid in patients who unexpectedly deteriorate rather than improve with haemodialysis may help in averting potentially severe complications due to errors in the concentrate selection. Conductivity cell devises are not suitable for the control of the acid-base composition of the dialysis fluid (dialysate), therefore, monitoring of the dialysate pH in addition to conductivity should become part of the equipment in haemodialysis machines.

Urate crystals induce NLRP3 inflammasome-dependent IL-1ß secretion and proliferation in isolated primary human T-cells.

BACKGROUND: Urate through NOD-like receptor family, pyrin domain containing 3 (NLRP3) inflammasome-dependent caspase-1 activation stimulates macrophages to secrete inteleukin-1ß (IL-1ß). Urate also enhances adaptive immunity indirectly through its effect on antigen presenting cells. In this study, the direct effect of urate on isolated primary human T-cells was evaluated. METHODS: Isolated T-cells were cultured with or without monosodium urate crystals in the presence or not of the NLRP3 inflammasome inhibitor glyburide. Activated cleaved caspase-1 was assessed by means of western blotting, whereas caspase-1 activity was measured colorimetrically in the cell lysates. IL-1ß was measured in the supernatants by means of enzyme-linked immunosorbent assay. T-cell proliferation was assessed by means of bromodeoxyuridine labelling and immunoenzymatic detection. RESULTS: Urate induced caspase-1 activation and IL-1ß release by T-cells. It also induced proliferation of T-cells. Glyburide inhibited urate-induced caspase-1 activation, IL-1ß secretion and proliferation. CONCLUSIONS: Urate, a well defined danger signal, stimulates directly human T-cells in a NLRP3 infmmasomela-dependent way. The subsequent IL-1ß secretion could enhance inflammation, whereas expansion of T-cell clones could facilitate a subsequent adaptive immune response. Hippokratia 2015, 19 (1): 41-46.