Longevity of anti-spike and anti-nucleocapsid antibodies after COVID-19 in solid organ transplant recipients compared to immunocompetent controls.

Solid organ transplant recipients (SOTRs) are on lifelong immunosuppression, which may interfere with adaptive immunity to COVID-19. The data on dynamics and duration of antibody response in SOTRs are limited. This longitudinal study examined the longevity of both anti-spike (S)- and anti-nucleocapsid (N)-specific IgG antibodies after COVID-19 in SOTRs compared to matched immunocompetent persons. SOTRs (n = 65) were matched with controls (n = 65) for COVID-19 disease severity, age, and sex in order of priority. Serum-IgG antibodies against N and S antigens of SARS-CoV-2 were analyzed. At 1 and 9 months after COVID-19, anti-S-IgG detectability decreased from 91% to 82% in SOTRs versus 100% to 95% in controls, whereas the anti-N-IgG decreased from 63% to 29% in SOTRs versus 89% to 46% in controls. A matched paired analysis showed SOTRs having significantly lower levels of anti-N-IgG at all time points (1 month p = .007, 3 months p < .001, 6 months p = .019, and 9 months p = .021) but not anti-S-IgG at any time points. A mixed-model analysis confirmed these findings except for anti-S-IgG at 1 month (p = .005) and identified severity score as the most important predictor of antibody response. SOTRs mount comparable S-specific, but not N-specific, antibody responses to SARS-CoV-2 infection compared to immunocompetent controls.

Status of periodontal health in German patients suffering from chronic kidney disease-Data from the GCKD study.

AIM: To assess the prevalence and severity of periodontitis in patients with moderate chronic kidney disease (CKD) and comparing the results with the self-reported periodontitis awareness of the study subjects. MATERIAL AND METHODS: The periodontal status of 270 patients with moderate CKD randomly selected from a cohort of 5,217 subjects participating in the prospective observational German Chronic Kidney Disease (GCKD) project was analysed by recording bleeding on probing (BOP), probing pocket depth (PPD) and clinical attachment level (CAL). Furthermore, the awareness of the study subjects of their periodontal conditions was evaluated by a self-reported questionnaire. RESULTS: 24.4% of the CKD study patients showed no or only mild signs of periodontal disease, 47.6% displayed moderate and 27% severe periodontitis. Questionnaire data revealed that 62.3% of the study subjects with severe periodontitis were not aware of the presence of the disease, 44.4% denied having received any systematic periodontal therapy so far, although 50% of them indicated to visit their dentist regularly for professional tooth cleanings. CONCLUSION: While the clinical study data confirm an increased prevalence of periodontitis in CKD patients, their self-reported awareness of periodontitis was low.

Association Between Dietary Patterns and Kidney Function in Patients With Chronic Kidney Disease: A Cross-Sectional Analysis of the German Chronic Kidney Disease Study.

OBJECTIVE: In the general population, "healthy" dietary patterns are associated with improved health outcomes, but data on associations between observance of specific dietary patterns and kidney function in patients with chronic kidney disease (CKD) are sparse. METHODS: Dietary intake was evaluated using food frequency questionnaires in patients with moderately severe CKD under nephrology care enrolled into the observational multicenter German CKD study. The Dietary Approaches to Stop Hypertension (DASH) diet score, Mediterranean diet score, and German Food Pyramid Index (GFPI) were calculated and their association with estimated glomerular filtration rate (eGFR) and albuminuria was assessed by multivariable linear regression analysis, adjusted for gender, age, body mass index, energy intake, smoking status, alcohol intake, education, high-density lipoprotein-cholesterol (HDL- cholesterol), low-density lipoprotein-cholesterol (LDL-cholesterol), hypertension, and diabetes mellitus. RESULTS: A total of 2,813 patients (41% women; age 60.1 ± 11.6 years) were included in the analysis. High DASH diet score and GFPI were associated with lower systolic blood pressure and lower intake of antihypertensive medication, higher HDL, and lower uric acid levels. Mediterranean-style diet was associated with lower prevalence of diabetes mellitus. Higher DASH and Mediterranean diet scores were associated with higher eGFR (ß-coefficient = 1.226, P < .001; ß-coefficient = 0.932, P = .007, respectively). In contrast, GFPI was not associated with eGFR. For the individual components of the dietary patterns, higher intake of nuts and legumes, cereals, fish, and polyunsaturated fats was associated with higher eGFR and higher intake of dairy, composed of low- and whole-fat dairy, was associated with lower eGFR. No association was found between dietary patterns and albuminuria. CONCLUSION: Higher observance of the DASH or Mediterranean diet, but not German food pyramid recommendations, was associated with higher eGFR among patients with CKD. Improving dietary habits may offer an opportunity to better control comorbidities and kidney function decline in patients with CKD.

Low prevalence of occult hepatitis B virus infection in chronic haemodialysis and kidney transplant patients.

BACKGROUND: Occult hepatitis B virus infection (OBI) is defined as the presence of hepatitis B virus (HBV) DNA in serum and/or liver in HBsAg-negative patients. We investigated the prevalence of OBI in large chronic haemodialysis (CHD) and kidney transplant recipients (KTxR) cohorts, including determination of HBV DNA in peripheral blood mononuclear cells (PBMCs). METHODS: HBV DNA was determined in both serum and PBMCs in 417 CHD patients, 417 KTxR, 20 HBsAg-positive non-CHD non-KTx patients (positive controls) and 40 HBsAg-negative healthy subjects (negative controls). RESULTS: Chronic haemodialysis group: two of 376 patients were HBsAg-positive. The 374 HBsAg-negative patients tested negative for HBV DNA in both serum and PBMCs. KTxR group: 14 of 417 patients were HBsAg-positive. One of 403 HBsAg-negative patients tested positive for HBV DNA in serum but not in PBMCs. Positive controls: six of 20 patients were under antiviral therapy and had negative HBV DNA in both serum and PBMCs. In 11 of 14 remaining patients, HBV DNA was detected in serum and in both serum and PBMCs in 3 patients. Negative controls: All 34 patients were anti-HBc-negative and HBV DNA-negative in both serum and PBMCs. In the long term, the only case of anti-HBc-negative OBI lost anti-HBs 5 years after inclusion in the study and showed HBV reactivation with HBsAg re-seroconversion. CONCLUSIONS: We found nil prevalence of OBI in CHD patients and a very low prevalence (<1%) in KTxR suggesting that routine screening for HBV DNA is not required in CHD population in our region. However, in KTxR, pretransplant screening with HBV DNA should be considered. Testing for HBV DNA in PBMCs does not seem to be of additional value.

Glycaemic control and antidiabetic therapy in patients with diabetes mellitus and chronic kidney disease - cross-sectional data from the German Chronic Kidney Disease (GCKD) cohort.

BACKGROUND: Diabetes mellitus (DM) is the leading cause of end-stage renal disease. Little is known about practice patterns of anti-diabetic therapy in the presence of chronic kidney disease (CKD) and correlates with glycaemic control. We therefore aimed to analyze current antidiabetic treatment and correlates of metabolic control in a large contemporary prospective cohort of patients with diabetes and CKD. METHODS: The German Chronic Kidney Disease (GCKD) study enrolled 5217 patients aged 18-74 years with an estimated glomerular filtration rate (eGFR) between 30-60 mL/min/1.73 m(2) or proteinuria >0.5 g/d. The use of diet prescription, oral anti-diabetic medication, and insulin was assessed at baseline. HbA1c, measured centrally, was the main outcome measure. RESULTS: At baseline, DM was present in 1842 patients (35 %) and the median HbA1C was 7.0 % (25(th)-75(th) percentile: 6.8-7.9 %), equalling 53 mmol/mol (51, 63); 24.2 % of patients received dietary treatment only, 25.5 % oral antidiabetic drugs but not insulin, 8.4 % oral antidiabetic drugs with insulin, and 41.8 % insulin alone. Metformin was used by 18.8 %. Factors associated with an HbA1C level >7.0 % (53 mmol/mol) were higher BMI (OR = 1.04 per increase of 1 kg/m(2), 95 % CI 1.02-1.06), hemoglobin (OR = 1.11 per increase of 1 g/dL, 95 % CI 1.04-1.18), treatment with insulin alone (OR = 5.63, 95 % CI 4.26-7.45) or in combination with oral antidiabetic agents (OR = 4.23, 95 % CI 2.77-6.46) but not monotherapy with metformin, DPP-4 inhibitors, or glinides. CONCLUSIONS: Within the GCKD cohort of patients with CKD stage 3 or overt proteinuria, antidiabetic treatment patterns were highly variable with a remarkably high proportion of more than 50 % receiving insulin-based therapies. Metabolic control was overall satisfactory, but insulin use was associated with higher HbA1C levels.

Implementation of the KDIGO guideline on lipid management requires a substantial increase in statin prescription rates.

The KDIGO guideline on lipid management in adult patients with chronic kidney disease (CKD) reflects a paradigm shift as proposals for statin use are based on cardiovascular risk rather than cholesterol levels. Statin use is now universally recommended in CKD patients 50 years and older, assuming a 10-year risk of coronary heart disease (CHD) of over 10%. Specific comorbidities or formal risk calculation are required for younger patients. It is unknown to which extent these new guidelines differ from previous practice. Here we analyzed statin use in the German Chronic Kidney Disease study of 5217 adult patients with moderately severe CKD under nephrological care enrolled shortly before publication of the new guideline. Accordingly, 407 patients younger than 50 years would be eligible for statins compared with the 277 patients treated so far, and all 4224 patients 50 years and older would be eligible compared with the 2196 already treated. Overall, guideline implementation would almost double statin prescription from 47 to 88%. Among patients 50 years and older currently not on a statin, an estimated 10-year CHD and atherosclerotic event risks over 10% were present in 68% and 82%, respectively. Thus, implementation of the new lipid guideline requires a substantial change in prescription practice, even in CKD patients under nephrological care. Based on comorbidities and risk estimates, the universal recommendation for statin use in CKD patients 50 years and older appears justified.

Prevalence of occult hepatitis C infection in chronic hemodialysis and kidney transplant patients.

BACKGROUND & AIMS: Detection of hepatitis C virus (HCV) RNA in peripheral blood mononuclear cells (PBMC) and/or hepatocytes in absence of HCV RNA in serum, designated as 'occult HCV infection', has been a matter of controversy in recent years. We investigated for the first time the prevalence of occult HCV infection in large cohorts of chronic hemodialysis (CHD) and kidney transplant (KTx) patients. METHODS: We enrolled 417 CHD patients, 417 KTx recipients and 2 control groups - 25 anti-HCV (antibody against HCV)-positive and HCV RNA-positive patients with chronic hepatitis C, and 40 anti-HCV-, HCV RNA-, and HBsAg-negative healthy subjects. HCV RNA was tested in serum and PBMC using a sensitive commercial assay. RESULTS: In CHD patients, the prevalence of anti-HCV was 3.6% (15/417) and of positive serum HCV RNA 2.4% (10/417). HCV RNA was detected in PBMC in 1/407 (0.25%) HCV serum RNA-negative patients ("occult HCV infection"). In KTx recipients, prevalence of anti-HCV was 4.8% (20/417) and of positive serum HCV RNA 4.6% (19/417). Occult HCV infection was found in 2/398 (0.5%) serum HCV RNA-negative patients. On a mean longitudinal follow-up of 30months of the 3 patients with occult HCV infection, there was no clinical or virological evidence of HCV infection. CONCLUSIONS: The prevalence of occult HCV infection was very low in our CHD and KTx patients, and it did not appear to be clinically relevant. Further studies in geographic populations with high HCV endemicity are required to clarify the significance of occult HCV infection in these patient groups.

Tocilizumab in chronic active antibody-mediated rejection: rationale and protocol of an in-progress randomized controlled open-label multi-center trial (INTERCEPT study).

BACKGROUND: Chronic active antibody-mediated rejection (caAMR) in kidney transplants is associated with irreversible tissue damage and a leading cause of graft loss in the long-term. However, the treatment for caAMR remains a challenge to date. Recently, tocilizumab, a recombinant humanized monoclonal antibody directed against the human interleukin-6 (IL-6) receptor, has shown promise in the treatment of caAMR. However, it has not been systematically investigated so far underscoring the need for randomized controlled studies in this area. METHODS: The INTERCEPT study is an investigator-driven randomized controlled open-label multi-center trial in kidney transplant recipients to assess the efficacy of tocilizumab in the treatment of biopsy-proven caAMR. A total of 50 recipients with biopsy-proven caAMR at least 12 months after transplantation will be randomized to receive either tocilizumab (n = 25) added to our standard of care (SOC) maintenance treatment or SOC alone (n = 25) for a period of 24 months. Patients will be followed for an additional 12 months after cessation of study medication. After the inclusion biopsies at baseline, protocol kidney graft biopsies will be performed at 12 and 24 months. The sample size calculation assumed a difference of 5 ml/year in slope of estimated glomerular filtration rate (eGFR) between the two groups for 80% power at an alpha of 0.05. The primary endpoint is the slope of eGFR at 24 months after start of treatment. The secondary endpoints include assessment of the following at 12, 24, and 36 months: composite risk score iBox, safety, evolution and characteristics of donor-specific antibodies (DSA), graft histology, proteinuria, kidney function assessed by measured GFR (mGFR), patient- and death-censored graft survival, and patient-reported outcomes that include transplant-specific well-being, adherence to immunosuppressive medications and perceived threat of the risk of graft rejection. DISCUSSION: No effective treatment exists for caAMR at present. Based on the hypothesis that inhibition of IL-6 receptor by tocilizumab will reduce antibody production and reduce antibody-mediated damage, our randomized trial has a potential to provide evidence for a novel treatment strategy for caAMR, therewith slowing the decline in graft function in the long-term. TRIAL REGISTRATION: ClinicalTrials.gov NCT04561986. Registered on September 24, 2020.

COVID-19 Outcomes and Vaccinations in Swedish Solid Organ Transplant Recipients 2020-2021: A Nationwide Multi-Register Comparative Cohort Study.

Increased COVID-19-related morbidity and mortality have been reported in solid organ transplant recipients (SOTRs). Most studies are underpowered for rigorous matching. We report infections, hospitalization, ICU care, mortality from COVID-19, and pertinent vaccination data in Swedish SOTRs 2020-2021. We conducted a nationwide cohort study, encompassing all Swedish residents. SOTRs were identified with ICD-10 codes and immunosuppressant prescriptions. Comparison cohorts were weighted based on a propensity score built from potential confounders (age, sex, comorbidities, socioeconomic factors, and geography), which achieved a good balance between SOTRs and non-SOTR groups. We included 10,372,033 individuals, including 9073 SOTRs. Of the SARS-CoV-2 infected, 47.3% of SOTRs and 19% of weighted comparator individuals were hospitalized. ICU care was given to 8% of infected SOTRs and 2% of weighted comparators. The case fatality rate was 7.7% in SOTRs, 6.2% in the weighted comparison cohort, and 1.3% in the unweighted comparison cohort. SOTRs had an increased risk of contracting COVID-19 (HR = 1.15 p < 0.001), being hospitalized (HR = 2.89 p < 0.001), receiving ICU care (HR = 4.59 p < 0.001), and dying (HR = 1.42 p < 0.001). SOTRs had much higher morbidity and mortality than the general population during 2020-2021. Also compared with weighted comparators, SOTRs had an increased risk of contracting COVID-19, being hospitalized, receiving ICU care, and dying. In Sweden, SOTRs were vaccinated earlier than weighted comparators. Lung transplant recipients had the worst outcomes. Excess mortality among SOTRs was concentrated in the second half of 2021.

Long and Short-Term Effects of Hypothermic Machine Perfusion vs. Cold Storage on Transplanted Kidneys from Expanded Criteria Donors-A Matched Comparison Study.

Hypothermic machine perfusion (HMP) has been shown to reduce delayed graft function (DGF)-rates in kidneys from expanded criteria donors (ECD) and may increase graft survival compared with static cold storage (SCS). This single-center, retrospective observational study aimed to evaluate this effect. The primary endpoint was the DGF-rate, defined as the use of dialysis in the first postoperative week, excluding the first 24 h. The main secondary endpoint was graft survival at 5 years. Recipients of ECD-kidneys between 2013 and 2021 with ≤2 grafts were included (n = 438). The SCS-kidneys were marginal-matched by propensity score to the HMP-group for donor age, cold ischemia time, and graft number. Multivariable adjusted analysis for confounders in the unmatched cohort and caliper-based ID-matching constituted sensitivity analyses. HMP showed a trend to lower DGF-rate in the marginal-matched comparison (9.2% vs. 16.1%, p = 0.063). This was strengthened by a significant benefit observed for HMP in both the sensitivity analyses: an adjusted OR of 0.45 (95% CI: 0.24; 0.84; p = 0.012) in the multivariable analysis and DGF-rate of 8.7% vs. 17.4% (p = 0.024) after ID-matching. The 5-year graft survival rate was >90% in both groups, with no benefit using HMP (HR = 0.79; 95% CI:0.39-1.16; p = 0.52). Our results suggest that HMP may be effective in decreasing DGF-rates, however, without any significant benefit in graft survival.

Magnetic Resonance Imaging in Clinical Trials of Diabetic Kidney Disease.

Chronic kidney disease (CKD) associated with diabetes mellitus (DM) (known as diabetic kidney disease, DKD) is a serious and growing healthcare problem worldwide. In DM patients, DKD is generally diagnosed based on the presence of albuminuria and a reduced glomerular filtration rate. Diagnosis rarely includes an invasive kidney biopsy, although DKD has some characteristic histological features, and kidney fibrosis and nephron loss cause disease progression that eventually ends in kidney failure. Alternative sensitive and reliable non-invasive biomarkers are needed for DKD (and CKD in general) to improve timely diagnosis and aid disease monitoring without the need for a kidney biopsy. Such biomarkers may also serve as endpoints in clinical trials of new treatments. Non-invasive magnetic resonance imaging (MRI), particularly multiparametric MRI, may achieve these goals. In this article, we review emerging data on MRI techniques and their scientific, clinical, and economic value in DKD/CKD for diagnosis, assessment of disease pathogenesis and progression, and as potential biomarkers for clinical trial use that may also increase our understanding of the efficacy and mode(s) of action of potential DKD therapeutic interventions. We also consider how multi-site MRI studies are conducted and the challenges that should be addressed to increase wider application of MRI in DKD.

Long-term Course of Kidney Function in Uterus Transplant Recipients Under Treatment With Tacrolimus and After Transplantectomy: Results of the First Clinical Cohort.

Background: Chronic kidney disease is common after non-renal solid organ transplantation, mainly secondary to calcineurin inhibitors toxicity. Uterus transplantation (UTx) is an innovative treatment for women with absolute uterine factor infertility. UTx is exclusive because it is transient with the absence of lifelong immunosuppression and is performed in young healthy participants. Therefore, UTx provides a unique setting for evaluating the effect of time-limited calcineurin inhibitors treatment on recipients' kidney function. Methods: In the first UTx cohort worldwide, we studied kidney function using estimated glomerular filtration rate (eGFR) in 7 women over a median follow-up of 121 (119-126) mo. Results: Median eGFR (mL/min/1.73 m2) of the cohort was 113 at UTx, which declined to 74 during month 3, 71 at months 10-12, 76 at hysterectomy (HE), and 83 at last follow-up. Median duration of tacrolimus exposure was 52 (22-83) mo, and median trough levels (µg/L) were 10 during month 3 and 5.8 at HE. Between UTx and month 3, decline in kidney function was observed in all 7 participants with a median eGFR slope for the whole cohort of -24 mL/min/1.73 m2, which declined further by -4 mL/min/1.73 m2 until months 10-12. Thereafter, eGFR slope improved in 3 participants, remained stable in 3, and worsened in 1 until HE/tacrolimus discontinuation, after which it improved in 2. Eventually, between UTx and last follow-up, 4 of 7 participants had a decline in their eGFR, the median annual eGFR slope being negative at -1.9 mL/min/1.73 m2/y for the whole group. Conclusions: Kidney function declined in all recipients early after UTx followed by a persistent long-term decrease in majority, despite transplantectomy and discontinuation of immunosuppression. Thus, UTx may incur an increased risk of chronic kidney disease even in this young and healthy population, highlighting the importance of close surveillance of kidney function and minimization of tacrolimus exposure.

Difficult-to-Treat Rejections in Kidney Transplant Recipients: Our Experience with Everolimus-Based Quadruple Maintenance Therapy.

All chronic and treatment-resistant acute rejections are "difficult-to-treat" and lead to progressive loss of graft function in kidney transplant recipients (KTR), as no effective treatment exists for such rejections to date. We review our experience with a novel strategy to treat such rejections by adding everolimus as a "rescue" to conventional triple maintenance therapy with prednisolone, mycophenolate mofetil and calcineurin inhibitor. We retrospectively analysed data in 28 KTR who received everolimus-based quadruple therapy at our institution for biopsy-proven chronic active T cell-mediated or antibody-mediated rejection (n = 19) or treatment-resistant acute rejections (n = 9) between 2011-2017. The primary outcome was 5-year death-censored graft survival. Main secondary outcomes were response to treatment defined by stable or improved graft function, 5-year patient survival and discontinuation rate of treatment. The Kaplan-Meier estimate for 5-year death-censored graft survival was 79% in all patients, 90% for patients with chronic active T cell-mediated rejections, 78% for chronic active antibody-mediated rejection and 67% for acute rejections. Response to treatment was achieved in 43% and 5-year patient survival was 94%. Treatment was stopped in 12 (43%) patients due to adverse events. Everolimus-based maintenance quadruple therapy, despite high rate of everolimus discontinuation due to adverse events, may be a valid approach in a subset of kidney transplant recipients with such difficult-to-treat rejections, which otherwise would lead to a high rate of graft loss.

The German Chronic Kidney Disease (GCKD) study: design and methods.

BACKGROUND: Chronic kidney disease (CKD) is increasingly recognized as a global health problem. The conditions leading to CKD, the health impact of CKD and the prognosis differ markedly between affected individuals. In particular, renal failure and cardiovascular mortality are competing risks for CKD patients. Opportunities for targeted intervention are very limited so far and require an improved understanding of the natural course of CKD, of the risk factors associated with various clinical end points and co-morbidities as well as of the underlying pathogenic mechanisms. METHODS: The German Chronic Kidney Disease (GCKD) study is a prospective observational national cohort study. It aims to enrol a total of 5000 patients with CKD of various aetiologies, who are under nephrological care, and to follow them for up to 10 years. At the time of enrolment, male and female patients have an estimated glomerular filtration rate (eGFR) of 30-60 mL/min×1.73 m2 or overt proteinuria in the presence of an eGFR>60 mL/min×1.73 m2. Standardized collection of biomaterials, including DNA, serum, plasma and urine will allow identification and validation of biomarkers associated with CKD, CKD progression and related complications using hypothesis-driven and hypothesis-free approaches. Patient recruitment and follow-up is organized through a network of academic nephrology centres collaborating with practising nephrologists throughout the country. CONCLUSIONS: The GCKD study will establish one of the largest cohorts to date of CKD patients not requiring renal replacement therapy. Similarities in its design with other observational CKD studies, including cohorts that have already been established in the USA and Japan, will allow comparative and joint analyses to identify important ethnic and geographic differences and to enhance opportunities for identification of relevant risk factors and markers.

A Randomized Controlled Trial on Safety of Steroid Avoidance in Immunologically Low-Risk Kidney Transplant Recipients.

INTRODUCTION: Steroid-based immunosuppression after transplantation increases the risk of post-transplant diabetes mellitus (PTDM), with adverse effects on patient and graft survival. In the SAILOR study, we investigated the safety and efficacy of complete steroid avoidance in immunologically low-risk kidney recipients without diabetes on the current standard-of-care maintenance regimen with tacrolimus/mycophenolate mofetil (MMF). METHODS: In this 2-year, multicenter, open-label trial, a total of 222 patients were randomized to receive either steroid avoidance protocol (tacrolimus/MMF/antithymocyte globulin [ATG] induction [n = 113]) or steroid maintenance protocol (tacrolimus/MMF/prednisolone/basiliximab-induction [n = 109]). RESULTS: At 1 year, no significant differences were found between steroid avoidance and steroid maintenance arms in the incidence of PTDM, the primary end point (12.4% vs. 18.3%, respectively, P = 0.30, CI: 16.3-4.4), or in overall biopsy-proven rejections (15% vs. 13.8%, respectively, P = 0.85). At 2 years, the composite end point of freedom from acute rejection, graft loss, and death (81% vs. 85%, respectively, P = 0.4), kidney function, or adverse events was comparable between the 2 arms. Moreover, 63.9% of the patients in the steroid avoidance arm remained free from steroids at 2 years. CONCLUSION: The SAILOR study provides further evidence for the feasibility, safety, and efficacy of early steroid-free treatment at 2 years in immunologically low-risk kidney recipients with tacrolimus/MMF maintenance regimen.

Multiparametric magnetic resonance imaging allows non-invasive functional and structural evaluation of diabetic kidney disease.

Background: We sought to develop a novel non-contrast multiparametric MRI (mpMRI) protocol employing several complementary techniques in a single scan session for a comprehensive functional and structural evaluation of diabetic kidney disease (DKD). Methods: In the cross-sectional part of this prospective observational study, 38 subjects ages 18‒79 years with type 2 diabetes and DKD [estimated glomerular filtration rate (eGFR) 15‒60 mL/min/1.73 m2] and 20 age- and gender-matched healthy volunteers (HVs) underwent mpMRI. Repeat mpMRI was performed on 23 DKD subjects and 10 HVs. By measured GFR (mGFR), 2 DKD subjects had GFR stage G2, 16 stage G3 and 20 stage G4/G5. A wide range of MRI biomarkers associated with kidney haemodynamics, oxygenation and macro/microstructure were evaluated. Their optimal sensitivity, specificity and repeatability to differentiate diabetic versus healthy kidneys and categorize various stages of disease as well as their correlation with mGFR/albuminuria was assessed. Results: Several MRI biomarkers differentiated diabetic from healthy kidneys and distinct GFR stages (G3 versus G4/G5); mean arterial flow (MAF) was the strongest predictor (sensitivity 0.94 and 1.0, specificity 1.00 and 0.69; P = .04 and .004, respectively). Parameters significantly correlating with mGFR were specific measures of kidney haemodynamics, oxygenation, microstructure and macrostructure, with MAF being the strongest univariate predictor (r = 0.92; P < .0001). Conclusions: A comprehensive and repeatable non-contrast mpMRI protocol was developed that, as a single, non-invasive tool, allows functional and structural assessment of DKD, which has the potential to provide valuable insights into underlying pathophysiology, disease progression and analysis of efficacy/mode of action of therapeutic interventions in DKD.

Renin-angiotensin blocker use is associated with improved cardiovascular mortality in Indian patients with mild-moderate chronic kidney disease-findings from the ICKD study.

Introduction: Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin receptor blockers (ARB) are the antihypertensive drug class of choice in patients with chronic kidney disease (CKD). Head-to-head comparisons of the renal or non-renal outcomes between ACEI/ARB users and nonusers have not been conducted in all population groups. We examined the renal and cardiovascular outcomes in users and nonusers enrolled in the Indian Chronic Kidney Disease (ICKD) Study. Methods: A total of 4,056 patients with mild-moderate CKD were studied. Patients were categorized as ACEI/ARB users or nonusers. Major adverse kidney events [ESKD (end stage kidney disease), ≥50% decline in eGFR and kidney death], all-cause mortality, and cardiovascular mortality were analyzed over a median follow-up period of 2.64 (1.40, 3.89) years between the two groups. Results: Out of a total of 4,056 patients, 3,487 (87%) were hypertensive. The adjusted sub-hazard ratio (SHR) and 95 % CI for ACEI /ARB users was 0.85 (0.71, 1.02) for MAKE, 0.80 (0.64, 0.99) for a 50% decline in eGFR, and 0.72 (0.58, 0.90) for ESKD. For cardiovascular mortality, ACEI/ARB users were at lower risk (SHR = 0.55, 95% CI: 0.34, 0.88). Diuretic users were at increased risk of all-cause mortality (HR = 1.95, 95% CI: 1.50, 2.53) and cardiovascular mortality (adjusted SHR = 1.73, 95% CI: 1.09, 2.73). There was non-significant association between the use of other antihypertensives and any of the end points. Discussion: ACEI/ARB use is associated with slower rate of decline in eGFR in those with CKD stage 1-3. ACEI/ARB users had a significantly lower risk of renal outcomes, and cardiovascular mortality.

Educational Attainment Is Associated With Kidney and Cardiovascular Outcomes in the German CKD (GCKD) Cohort.

Introduction: Prospective data on impact of educational attainment on prognosis in patients with chronic kidney disease (CKD) are scarce. We investigated the association between educational attainment and all-cause mortality, major adverse cardiovascular (CV) events (MACEs), kidney failure requiring dialysis, and CKD etiology. Methods: Participants (N = 5095, aged 18-74 years) of the ongoing multicenter German Chronic Kidney Disease (GCKD) cohort, enrolled on the basis of an estimated glomerular filtration rate (eGFR) of 30 to 60 ml/min (stages G3, A1-A3) or overt proteinuria (stages G1-G2, A3), were divided into 3 categories according to their educational attainment and were followed for 6.5 years. Results: Participants with low educational attainment (vs. high) had a higher risk for mortality (hazard ratio [HR] 1.48, 95% CI: 1.16-1.90), MACE (HR 1.37, 95% CI: 1.02-1.83), and kidney failure (HR 1.54, 95% CI: 1.15-2.05). Mediators between low educational attainment and mortality were smoking, CV disease (CVD) at baseline, low income, higher body mass index, and higher serum levels of CRP, high-density lipoprotein cholesterol, uric acid, NGAL, BAP, NT-proBNP, OPN, H-FABP, and urea. Low educational attainment was positively associated with diabetic nephropathy (odds ratio [OR] 1.65, 95% CI: 1.36-2.0) and CKD subsequent to acute kidney injury (OR 1.56, 95% CI: 1.03-2.35), but negatively associated with IgA nephropathy (OR 0.68, 95% CI: 0.52-0.90). Conclusion: Low educational attainment is associated with adverse outcomes and CKD etiology. Lifestyle habits and biomarkers mediate associations between low educational attainment and mortality. Recognition of the role of educational attainment and the associated health-relevant risk factors is important to optimize the care of patients with CKD and improve prognosis.

The Indian Chronic Kidney Disease (ICKD) study: baseline characteristics.

BACKGROUND: Chronic kidney disease (CKD) is an important cause of morbidity and mortality worldwide. There is a lack of information on epidemiology and progression of CKD in low-middle income countries. The Indian Chronic Kidney Disease (ICKD) study aims to identify factors that associate with CKD progression, and development of kidney failure and cardiovascular disease (CVD) in Indian patients with CKD. METHODS: ICKD study is prospective, multicentric cohort study enrolling patients with estimated glomerular filtration rate (eGFR) 15-60 mL/min/1.73 m2, or >60 mL/min/1.73 m2 with proteinuria. Clinical details and biological samples are collected at annual visits. We analysed the baseline characteristics including socio-demographic details, risk factors, disease characteristics and laboratory measurements. In addition, we compared characteristics between urban and rural participants. RESULTS: A total of 4056 patients have been enrolled up to 31 March 2020. The mean ± SD age was 50.3 ± 11.8 years, 67.2% were males, two-thirds of patients lived in rural areas and the median eGFR was 40 mL/min/1.73 m2. About 87% were hypertensive, 37% had diabetes, 22% had CVD, 6.7% had past history of acute kidney injury and 23% reported prior use of alternative drugs. Diabetic kidney disease, chronic interstitial nephritis (CIN) and CKD-cause unknown (CKDu) were the leading causes. Rural participants had more occupational exposure and tobacco use but lower educational status and income. CIN and unknown categories were leading causes in rural participants. CONCLUSIONS: The ICKD study is the only large cohort study of patients with mild-to-moderate CKD in a lower middle income country. Baseline characteristics of study population reveal differences as compared with other cohorts from high-income countries.