Management and Outcomes of Kidney Transplant Candidates With Severe Pulmonary Hypertension: A Single-center Strategy and Experience.

Background: Severe pulmonary hypertension (PH) is associated with high mortality posttransplant and thus is considered a contraindication to kidney transplantation. In this study, we describe the pretransplant management and posttransplant outcomes in patients with severe PH using a multidisciplinary approach. Methods: Between 11 of 2013 and 8 of 2022, we identified all patients with severe PH on initial pretransplant workup who underwent ultrafiltration (UF) or medical therapy for PH before transplant. Posttransplant we evaluated the perioperative course, renal function, graft, and patient survival. We compared survival to those who remained waitlisted or were delisted. Results: Three-two patients (mean age = 55.03 ± 10.22 y) diagnosed with severe PH on pretransplant screening echocardiogram. Thirty patients (94%) were subjected to a median of 4 (range, 3-8) UF sessions with an average weight loss of 4.33 ± 2.6 kg. Repeat assessment of PH revealed a decline in mean pulmonary artery systolic pressure from 67 ± 12 mm Hg to 43 ± 13 mm Hg (P < 0.0001). Seventeen patients (53%) received a kidney transplant. The mean estimated Glomerular Filtration Rate at 3, 6, 9, and 12 mo was 72 ± 27, 72 ± 28, 75 ± 29, and 75 ± 29 mL/min/1.73 m2. Among, those who underwent transplantation both graft and patient survival was 100% at 1-y posttransplant. Overall, since the UF intervention, at a median follow-up of 88 ± 12 mo those transplanted had a patient survival of 88% while those who remained on dialysis had a survival of 53% (P = 0.0003). Conclusion: In this single-center study, we report postcapillary PH can be a significant contributor to elevations in pulmonary artery systolic pressure. Using a multidisciplinary approach, PH can improve with volume removal and phosphodiesterase 5 inhibitors therapy leading to a successful posttransplant outcome.

Use of belatacept in kidney transplantation: what's new?

PURPOSE OF REVIEW: The advent of calcineurin inhibitors have led to a significant improvement in short term outcomes after kidney transplantation. However, long term outcomes are hindered by the cardiovascular, metabolic and chronic renal toxicity associated with these agents. Belatacept is a selective T cell costimulation blocker that is approved for prevention of rejection in kidney transplantation, and has been associated with favorable cardiovascular, metabolic and renal outcomes in kidney transplant recipients. This review provides an overview of recent updates in the use of belatacept in kidney transplant recipients. RECENT FINDINGS: Belatacept may be a safe alternative to calcineurin inhibitors for select kidney transplant populations. Patients converted to belatacept from a calcineurin inhibitor-based immunosuppression generally experience improvement in renal function, and may be less likely to develop de novo donor specific antibodies or new onset diabetes after transplantation. Although, belatacept based immunosuppression may increase the risk of early acute cellular rejection, it may however be beneficial in stabilization of long-term renal function and improvement in inflammation in patients with chronic active antibody mediated rejection. These benefits need to be counterweighed with risks of lack of response to severe acute respiratory syndrome coronavirus 2 vaccination and other adverse infectious outcomes. SUMMARY: Belatacept may be an alternative to calcineurin inhibitors and may contribute to improved long term metabolic and allograft outcomes in kidney transplant recipients. Careful selection of patients for belatacept-based immunosuppression is needed, to obviate the risk of acute rejection shown in clinical studies.

Correlation of Donor-derived Cell-free DNA With Histology and Molecular Diagnoses of Kidney Transplant Biopsies.

BACKGROUND: Circulating donor-derived cell-free DNA (cfDNA), a minimally invasive diagnostic tool for kidney transplant rejection, was validated using traditional histology. The molecular microscope diagnostic system (MMDx) tissue gene expression platform may provide increased precision to traditional histology. METHODS: In this single-center prospective study of 208 biopsies (median = 5.8 mo) posttransplant, we report on the calibration of cfDNA with simultaneous biopsy assessments using MMDx and histology by area under the curve (AUC) analyses for optimal criterion, as well as for, previously published cfDNA cutoffs ≤ 0.21% to "rule-out" rejection and ≥1% to "rule-in" rejection. RESULTS: There were significant discrepancies between histology and MMDx, with MMDx identifying more antibody-mediated rejection (65; 31%) than histology (43; 21%); the opposite was true for T cell-mediated rejection [TCMR; histology: 27 (13%) versus MMDx: 13 (6%)]. Most of the TCMR discrepancies were seen for histologic borderline/1A TCMR. AUC for cfDNA and prediction of rejection were slightly better with MMDx (AUC = 0.80; 95% CI: 0.74-0.86) versus histology (AUC = 0.75; 95% CI: 0.69-0.81). A cfDNA ≤ 0.21% had similar sensitivity (~91%) to "rule-out" rejection by histology and MMDx. Specificity was slightly higher with MMDx (92%) compared with histology (85%) to "rule-in" rejection using cfDNA criterion ≥1%. Strong positive quantitative correlations were observed between cfDNA scores and molecular acute kidney injury for both "rejection" and "nonrejection" biopsies. CONCLUSIONS: Molecular diagnostics using tissue gene expression and blood-based donor-derived cell-free DNA may add precision to some cases of traditional histology. The positive correlation of cfDNA with molecular acute kidney injury suggests a dose-dependent association with tissue injury irrespective of rejection characteristics.

Clinical outcomes from the Assessing Donor-derived cell-free DNA Monitoring Insights of kidney Allografts with Longitudinal surveillance (ADMIRAL) study.

The use of routine monitoring of donor-derived cell-free DNA (dd-cfDNA) after kidney transplant may allow clinicians to identify subclinical allograft injury and intervene prior to development of clinically evident graft injury. To evaluate this, data from 1092 kidney transplant recipients monitored for dd-cfDNA over a three-year period was analyzed to assess the association of dd-cfDNA with histologic evidence of allograft rejection. Elevation of dd-cfDNA (0.5% or more) was significantly correlated with clinical and subclinical allograft rejection. dd-cfDNA values of 0.5% or more were associated with a nearly three-fold increase in risk development of de novo donor-specific antibodies (hazard ratio 2.71) and were determined to be elevated a median of 91 days (interquartile range of 30-125 days) ahead of donor specific antibody identification. Persistently elevated dd-cfDNA (more than one result above the 0.5% threshold) predicted over a 25% decline in the estimated glomerular filtration rate over three years (hazard ratio 1.97). Therefore, routine monitoring of dd-cfDNA allowed early identification of clinically important graft injury. Biomarker monitoring complemented histology and traditional laboratory surveillance strategies as a prognostic marker and risk-stratification tool post-transplant. Thus, persistently low dd-cfDNA levels may accurately identify allograft quiescence or absence of injury, paving the way for personalization of immunosuppression trials.

Outcomes of short-duration antiviral prophylaxis for hepatitis C positive donor kidney transplants.

Trials describing 4- to 12-week courses of direct-acting antiviral drugs (DAAs) to treat hepatitis C virus (HCV) transmission from infected donors to uninfected kidney transplant recipients (D+/R- transplants) may be limited in "real-world" application by costs and delayed access to DAAs. We previously reported HCV transmission of 13% among D+/R- transplants with 2- to 4-day pangenotypic sofosbuvir/velpatasvir (SOF/VEL) perioperative prophylaxis, where one patient with HCV transmission was a nonresponder to first-line full-course DAA. Here, we report new data with a 7-day prophylaxis protocol (N = 50), as well as cumulative treatment and outcome data on all HCV D+/R- transplants (N = 102). Overall, nine patients (9/102; 9%; 95% CI: 5%-16%) developed HCV transmission, with a significant decline noted in the 7-day group (2/50; 4%; 95% CI: 0%-13%) compared with 2- to 4-day prophylaxis (7/52; 13%; 95% CI: 5%-25%). All patients with HCV transmission achieved sustained virologic response post full-course therapy (including one nonresponder from initial trial). A 1:1 matched analysis (N = 102) with contemporary HCV D-/R- transplants (controls) showed that although the pretransplant wait time was significantly shorter for D+/R- compared with D-/R- (mean: 1.8 vs. 4.4 years; p < .001), there were no differences in infections, rejection, development of de novo donor-specific antibody, or transplant outcomes up to 6 months of transplant.

Coronavirus Disease 2019 Viremia, Serologies, and Clinical Course in a Case Series of Transplant Recipients.

Here we report a single-center cohort of 6 patients (4 kidney only, and 2 simultaneous liver/kidney transplants) diagnosed with COVID-19 at a median of 1.9 years (range = 0.2-9.3 years) post transplant. Five (of 6) patients required inpatient admission, 2 patients (mortality = 33%) died. Among those with mortality, an increased concentration of inflammatory biomarkers (interleukin-6 and C-reactive protein) was noted with a lack of response to interleukin-6 blockade, remdesivir, and/or convalescent plasma. None of the kidney-only transplants (4/6; 67%) had elevation in plasma donor-derived cell-free DNA above the previously published cut-off of 1%, suggesting absence of significant allo-immune injury. Four (of 5) admitted patients had detectable SARS-CoV-2 (severe acute respiratory syndrome-coronavirus 2) in blood on samples obtained at/during hospitalization. Of the 4 discharged patients, 2 patients with undetectable virus on repeat nasopharyngeal swabs had seroconversion with positive SARS-CoV-2 IgG formation at 30 to 48 days post infection. One patient had prolonged shedding of virus on nasopharyngeal swab at 28 days post discharge despite lack of symptoms. In this preliminary report, we find that immunocompromised transplant patients had higher rates of RNAemia (67%) than reported in the general population (15%), seeming absence of allo-immune injury despite systemic inflammation, and formation of IgG overtime after recovery from infection.

Lack of Histological and Molecular Signature Response to Tocilizumab in Kidney Transplants with Chronic Active Antibody Mediated Rejection: A Case Series.

Background: Traditional therapies for caAbMR have unclear efficacy with significant side effects in recipients of kidney transplants (KTs). A recent single-center case series suggested tocilizumab (TCZ) could stabilize renal function and improve microvascular inflammation. Here we report our findings of the use of TCZ in patients with caAbMR. Methods: Ten adult recipients of KTs with biopsy-proven caAbMR were treated with TCZ at 8 mg/kg per month. Patients were monitored for adverse events, and therapy was interrupted in the setting of serious infections. Six patients (60%) underwent post-treatment biopsies. Results: Patients (mean age of 43 years) were initiated on TCZ at a median of 36 months post-KT. A majority of patients were black (70%), underwent regrafts (40%), and were sensitized (mean cPRA=41%). Patients received a median of six doses of TCZ (range=3-10). At a median follow-up of 12 months (range=8-24 months), renal function did not show improvement (mean eGFR, 42±18 ml/min per 1.73 m2 to 37±24 ml/min per 1.73 m2; P=0.27). The slope of decline in eGFR remained unchanged (-0.14±0.9 to -0.33±1.1; P=0.25). There was no improvement in mean MVI (g+ptc) (4.8±1.4 to 4.2±2.0; P=0.39) scores or Molecular Microscope Diagnostic System (MMDx) AbMR scores (0.79±0.17 to 0.78±0.26; P=0.86). There was a numeric worsening of chronicity (ci+ct) scores (2.5±0.8 to 3.3±1.7; P=0.38) and MMDx atrophy fibrosis scores (0.36±0.24 to 0.58±0.15; P=0.21). Patient survival was 90%, with one patient death due to complications from a hip infection. Overall death-censored graft survival was 80%, with two graft losses in patients who had recurrent infections requiring hospitalization. Conclusions: In this early experience, we report a lack of efficacy and toxicity with the use of TCZ for caAbMR. Prospective clinical trials are needed to clarify the role of IL-6 blockade and the possibility of increased incidence of infections in patients with caAbMR who are treated with TCZ.

Ultra-short duration direct acting antiviral prophylaxis to prevent virus transmission from hepatitis C viremic donors to hepatitis C negative kidney transplant recipients.

We conducted an adaptive design single-center pilot trial between October 2017 and November 2018 to determine the safety and efficacy of ultra-short-term perioperative pangenotypic direct acting antiviral (DAA) prophylaxis for deceased hepatitis C virus (HCV)-nucleic acid test (NAT) positive donors to HCV negative kidney recipients (D+/R-). In Group 1, 10 patients received one dose of SOF/VEL (sofusbuvir/velpatasvir) pretransplant and one dose on posttransplant Day 1. In Group 2A (N = 15) and the posttrial validation (Group 2B; N = 25) phase, patients received two additional SOF/VEL doses (total 4) on Days 2 and 3 posttransplant. Development of posttransplant HCV transmission triggered 12-week DAA therapy. For available donor samples (N = 27), median donor viral load was 1.37E + 06 IU/mL (genotype [GT]1a: 70%; GT2: 7%; GT3: 23%). Overall viral transmission rate was 12% (6/50; Group 1:30% [3/10]; Group 2A:13% [2/15]; Group 2B:4% [1/25]). For the 6 viremic patients, 5 (83%) achieved sustained virologic response (3 with first-line DAA therapy; and two after retreatment with second-line DAA). At a median follow-up of 8 months posttransplant, overall patient and allograft survivals were 98%, respectively. The 4-day strategy reduced viral transmission to 7.5% (3/40; 95% confidence interval [CI]: 1.8%-20.5%) and could result in avoidance of prolonged posttransplant DAA therapy for most D+/R - transplants.

Kidney allograft survival outcomes in combined intestinal-kidney transplant: An analysis of the UNOS/OPTN database 2000-2014.

BACKGROUND AND OBJECTIVES: Intestinal transplants carry a high morbidity/mortality. Kidney allograft outcomes after combined intestinal (IT) with kidney transplant (CIKT) remain largely uninvestigated. MATERIALS AND METHODS: The UNOS STAR database was queried to identify all such combined organ transplants from 2000 to 2015. RESULTS: Out of a total 2215 (51.4% peds vs 48.6% adults) intestinal transplants, 111 (5.0%) CIKT were identified (32.4% peds vs 67.6% adults). Over the study period of CIKT, a total of 45.9% of these cases died with a functioning kidney graft. DGF rate was 9.0%. The 1-year reported kidney acute rejection rate was 6.3%. For the entire CIKT population over the entire study era, the 1-, 3-, and 5-year unadjusted kidney graft survival was 57%, 39%, and 34%, while death-censored kidney graft survival was 93%, 90%, and 86%, respectively. Overall conditional 5-year kidney graft survival (defined as 1-year kidney graft survival) was 58%. Overall, patient survival was significantly lower in recipients of CIKT compared to intestinal transplant (IT) (P < .005); However, the 5-year conditional (1 year kidney graft) patient survival in adults was not significantly different between IT and CIKT overall (P = .194). CONCLUSIONS: Kidney allograft survival is primarily dependent on 1-year patient survival. Guidelines regarding allocation of kidney allografts in CIKT need to take into consideration utility and urgency.

Isolated pancreas rejections do not have an adverse impact on kidney graft survival whereas kidney rejections are associated with adverse pancreas graft survival in simultaneous pancreas kidney transplantation.

BACKGROUND AND OBJECTIVES: Diabetic Kidney Disease is associated with excessive mortality and morbidity. Simultaneous pancreas kidney transplantation (SPK) significantly improves quality of life and increases life expectancy of uremic diabetic patients. It is not known whether pancreas and kidney rejections in these transplant patients is concordant or discordant. DESIGN, SETTING, PARTICIPANTS, AND MEASUREMENTS: We analyzed clinical data on all SPK transplants performed between 2003 and 2014 at Indiana University to assess the impact of isolated or combined pancreas and kidney rejections on patient and allograft outcomes. The primary outcome of interest was kidney graft rejection within 1 year of pancreatic rejection and kidney survival in SPK patients with and without pancreatic rejection. RESULTS: Mean age of patients was 44 ± 9 years; 61.9% were males; 88% were Caucasians. A total of 23.8% of cases had rejection [8.7% pancreatic rejection alone (PA), 4.4% had concordant pancreas and kidney (PK) rejection, and 10.7% had kidney rejection alone(KA)]. PK had a worse effect on kidney graft survival than PA (p = 0.019). Neither pancreas rejection nor kidney rejection had an adverse effect on patient survival. However, both pancreas graft failure and kidney graft failure adversely affected patient survival. Tacrolimus levels were not significantly different in all groups over a 10 year period (p = 0.4584). CONCLUSIONS: Concordant pancreas kidney rejection is synergistically deleterious to kidney graft survival. Graft failure, not graft rejection, is adversely associated with patient survival.

Early Posttransplant Isolated v1 Lesion Does Not Need to Be Treated and Does Not Lead to Increased Fibrosis.

Acute vascular rejection (AVR) is characterized by intimal arteritis in addition to tubulitis and interstitial inflammation. It is associated with a poorer prognosis compared to tubulointerstitial rejection (AIR) and AVR is associated with a higher rate of graft loss than AIR. The prognosis and treatment of arteritis without tubulitis and interstitial inflammation (isolated v1 lesion) are still controversial. We report a case of a patient who had a biopsy of the kidney allograft for evaluation of slow graft function. The biopsy revealed an isolated v1 lesion. However, we chose not to augment immunosuppression. The patient's kidney allograft function improved over time with close monitoring. Repeat biopsy a year later showed no evidence of endothelialitis and relatively unchanged fibrosis and no other abnormalities. Although it is suggested that most cases of isolated v1 lesions will respond to corticosteroids or T cell depleting therapies, some cases will improve with conservative management. Further studies are needed to determine which cases could be managed conservatively.

Membranous nephropathy with crescents associated with levamisole-induced MPO-ANCA vasculitis.

ANCA-associated vasculitis (AAV) is the most common cause of crescentic rapidly progressive glomerulonephritis (GN). Levamisole used as an adulterant in cocaine is increasingly recognized as a cause of AAV. We report the case of a 50 year old woman with atypical anti-MPO AAV associated with cocaine use and exposure to levamisole. In addition to the clinical and pathologic findings of crescentic GN, the patient also had biopsy evidence of secondary membranous nephropathy (MN). Although AAV and MN have been reported previously in the same patient and both have been induced by drug exposures, this is the first report of MN in a patient with AAV likely induced by levamisole. We suggest that MPO can cause both pauci-immune vasculitis and secondary membranous nephropathy in some cases, as in cases of levamisole-adulterated cocaine use.

Acute oxalate nephropathy due to pancreatic atrophy in newly diagnosed pancreatic carcinoma.

Acute oxalate nephropathy can occur due to primary hyperoxaluria and secondary hyperoxaluria. The primary hyperoxalurias are a group of autosomal recessive disorders of endogenous oxalate overproduction. Secondary hyperoxaluria may occur as a result of excess dietary intake, poisoning with oxalate precursors (ethylene glycol), or enteric hyperoxaluria. The differential diagnosis of enteric hyperoxaluria includes inflammatory bowel disease, short bowel syndrome, bariatric surgery (with jejunoileal bypass or Roux-en-Y gastric bypass), celiac disease, partial colectomy, and chronic pancreatitis. The common etiology in all these processes is fat malabsorption, steatorrhea, saponification of calcium, and absorption of free oxalate. Hyperoxaluria causes increased urinary oxalate excretion, urolithiasis (promoted by hypovolemia, decreased urinary pH caused by metabolic acidosis, and decreased citrate and magnesium concentrations in urine), tubulointerstitial oxalate deposits, and tubulointerstitial nephritis. We report a rare case of acute oxalate nephropathy due to pancreatic atrophy and exocrine insufficiency caused by newly diagnosed pancreatic cancer.

Allergic Interstitial Nephritis Manifesting as a Striated Nephrogram.

Allergic interstitial nephritis (AIN) is an underdiagnosed cause of acute kidney injury (AKI). Guidelines suggest that AIN should be suspected in a patient who presents with an elevated serum creatinine and a urinalysis that shows white cells, white cell casts, or eosinophiluria. Drug-induced AIN is suspected if AKI is temporally related to the initiation of a new drug. However, patients with bland sediment and normal urinalysis can also have AIN. Currently, a definitive diagnosis of AIN is made by renal biopsy which is invasive and fraught with risks such as bleeding, infection, and hematoma. Additionally, it is frequently unclear when a kidney biopsy should be undertaken. We describe a biopsy proven case of allergic interstitial nephritis which manifested on contrast enhanced Magnetic Resonance Imaging (MRI) as a striated nephrogram. Newer and more stable macrocyclic gadolinium contrast agents have a well-demonstrated safety profile. Additionally, in the presentation of AKI, gadolinium contrast agents are safe to administer in patients who demonstrate good urine output and a downtrending creatinine. We propose that the differential for a striated nephrogram may include AIN. In cases in which the suspicion for AIN is high, this diagnostic consideration may be further characterized by contrast enhanced MRI.

Outcomes with retrievable inferior vena cava filters.

This was a retrospective study of 144 patients with retrievable inferior vena cava (IVC) filters inserted between 2004 and 2008 at a community/teaching hospital. The purpose was to evaluate the incidence of complications and the rate and success of retrieval. Retrieval of IVC filters was attempted in 14 of 144 (10%) patients at an average of 4.6 months. Retrieval was successful in 10 of 14 (71%). Within 6 months of insertion, retrieval was successful in 10 of 12 (83%). Unsuccessful attempts were at 3, 6, 8 and 9 months. Non-bleeding complications of IVC filters occurred in 12 of 144 (8.3%). Half (6 of 12) of the complications occurred after 3 months of insertion. Complications included IVC thrombosis in 3 (2.1%) (1 also had a new deep venous thrombosis [DVT]), a new DVT alone in 6 patients (4.2%), a new DVT with new pulmonary embolism (PE) in 1 patient (0.7%) and filter migration in 2 patients (1.3%). In conclusion, retrieval was attempted in only a small proportion of patients at a community/teaching hospital. Formalized guidelines for follow up may increase the proportion of patients in whom retrieval is attempted. Half of the complications of IVC filters could have been avoided with retrieval within 3 months.

Aerobic exercise in obese diabetic patients with chronic kidney disease: a randomized and controlled pilot study.

BACKGROUND: Patients with obesity, diabetes, and chronic kidney disease (CKD) are generally physically inactive, have a high mortality rate, and may benefit from an exercise program. METHODS: We performed a 24-week randomized controlled feasibility study comparing aerobic exercise plus optimal medical management to medical management alone in patients with type 2 diabetes, obesity (body mass index [BMI] > 30 kg/m2), and stage 2-4 CKD (estimated glomerular filtration rate [eGFR] 15-90 mL/min/1.73 m2 with persistent proteinuria). Subjects randomized to exercise underwent thrice weekly aerobic training for 6 followed by 18 weeks of supervised home exercise. The primary outcome variable was change in proteinuria. RESULTS: Seven subjects randomized to exercise and 4 control subjects completed the study. Exercise training resulted in an increase in exercise duration during treadmill testing, which was accompanied by slight but insignificant decreases in resting systolic blood pressure and 24-hour proteinuria. Exercise did not alter GFR, hemoglobin, glycated hemoglobin, serum lipids, or C-reactive protein (CRP). Caloric intake and body weight and composition also did not change with exercise training. CONCLUSION: Exercise training in obese diabetic patients with CKD is feasible and may have clinical benefits. A large-scale randomized controlled trial to determine the effects of exercise on renal functions, cardiovascular fitness, inflammation, and oxidative stress in diabetic patients with CKD is planned.

A comparison of aerobic exercise and resistance training in patients with and without chronic kidney disease.

The morbidity and mortality associated with chronic kidney disease (CKD) are primarily caused by atherosclerosis and cardiovascular disease, which may be in part caused by inflammation and oxidative stress. Aerobic exercise and resistance training have been proposed as measures to combat obesity, inflammation, endothelial dysfunction, oxidative stress, insulin resistance, and progression of CKD. In non-CKD patients, aerobic exercise reduces inflammation, increases insulin sensitivity, decreases microalbuminuria, facilitates weight loss, decreases leptins, and protects against oxidative injury. In nondialysis CKD, aerobic exercise decreases microalbuminuria, protects from oxidative stress, and may increase the glomerular filtration rate (GFR). Aerobic exercise in hemodialysis patients has been reported to enhance insulin sensitivity, improve lipid profile, increase hemoglobin, increase strength, decrease blood pressure, and improve quality of life. Resistance training, in the general population, decreases C-reactive protein, increases insulin sensitivity, decreases body fat content, increases insulin-like growth factor-1 (IGF-1), and decreases microalbuminuria. In the nondialysis CKD population, resistance training has been reported to reduce inflammation, increase serum albumin, maintain body weight, increase muscle strength, increase IGF-1, and increase GFR. Resistance training in hemodialysis increases muscle strength, increases physical functionality, and improves IGF-1 status. Combined aerobic exercise and resistance training during dialysis improves muscle strength, work output, cardiac fitness, and possibly dialysis adequacy. There is a need for more investigation on the role of exercise in CKD. If the benefits of aerobic exercise and strength training in non-CKD populations can be shown to apply to CKD patients as well, renal rehabilitation will begin to play an important role in the approach to the treatment, prevention, and slowed progression of CKD.