Minutes of an International Weekly Meeting on “Chronic Kidney Disease and Its Management”

Speaker: Dr DK Sinha, MD, DM Nephrology. Senior Consultant, Dept. of Nephrology, Heritage Hospitals, Varanasi, Uttar Pradesh

February 24, 2024 (Saturday, 9.30-10.30 am)

·         As the population grows older, the incidence of chronic kidney disease (CKD) is also rising. Most CKD patients are in stages 1 to 3.

·         Among adults aged 65 to 74 years, 20% of men and 25% of women have CKD. In persons older than 75 years, 40% of men and 60% of women may have CKD.

·         Around 14% of adults in US are estimated to have CKD. The incidence of CKD in the Indian population was determined to be 14% to 16% in the Screening and Early Evaluation of Kidney Disease (SEEK) study.

·         CKD is defined as abnormalities in structure and function, which have been present for more than 3 months.

·         Markers of CKD include albuminuria, abnormal urinary sediment, electrolyte abnormalities, histological abnormalities and structural abnormalities detected by imaging, or if the patient has persistent fall in estimated glomerular filtration rate (eGFR). 

·         There are five stages of CKD. Stage 3, which is mild to moderate kidney damage, has been further categorized as stage 3a and 3b. This stage of CKD is usually ignored as the test reports are very close to normal.

·         The extent of albuminuria is very important. It has been classified into A1 (urinary albumin-creatinine ratio [UACR] <30 mg/g), A2 (UACR 30-399 mg/g), and A3 (>300 mg/g).

·         eGFR and UACR are important in classification of CKD and also its prognosis. 

·         Most CKD patients do not reach the stage of end-stage renal disease (ESRD) as they usually succumb to complications such as cardiovascular (CV) and cerebrovascular events.

·         Patient’s history provides clues to the diagnosis of CKD. These include symptoms during urination, recent infection, skin rash or arthritis, any parenterally transmitted diseases, chronic diseases such as diabetes, hypertension, skin disease; past medical history such as nonsteroidal anti-inflammatory drug (NSAID) intake, past urologic evaluation, family history of kidney disease.

·         Majority of patients with CKD have diabetes (40%) and hypertension (27%). Hence, more attention has to be paid to manage these conditions. Other causes include glomerulonephritis (11%), interstitial nephritis (4%); around 18% cases may be due to other causes.

·         Factors associated with progression include cause of CKD, level of GFR, level of albuminuria, age, sex, race/ethnicity, elevated blood pressure (BP), hyperglycemia, dyslipidemia, smoking, obesity, history of cardiovascular disease (CVD), ongoing exposure to nephrotoxic agents.

·         Early treatment can make a difference in CKD. Intervention in the early stage of the disease may allow longer duration of dialysis-free life.

·         Approaches to preserving kidney function include symptom management, palliative care and kidney-preserving care.

·         Kidney-preserving care aims to slow progression of disease, prevent or delay diagnosis, and improve CV risk. The components of kidney-preserving care include diet and lifestyle, pharmacotherapy for disease progression, for CV risk management, and for other comorbidities such as bone health, anemia. Comprehensive care is needed to retard the progression of CKD.

·         A low protein diet is recommended. Protein intake should be lowered to 0.8 g/kg/day in adults with diabetes or without diabetes and GFR <30 mL/min/1.73 m². Protein intake >1.3 g/kg/day in adults with CKD at risk of progression should be avoided.

·         Salt intake should be lowered to <2 g/day of sodium, unless contraindicated.

·         CKD patients should be encouraged to undertake physical activity compatible with CV health and tolerance (at least 30 minutes 5 times in a week), achieve a healthy weight (body mass index [BMI] 20-25), and quit smoking.

·         Patients with type 1 diabetes should be screened annually starting 5 years after diagnosis, while type 2 diabetes patients should undergo yearly screening starting at diagnosis. Tests used for screening are eGFR and spot UACR.

·         Parameters used to define CKD are persistent UACR >30 mg/g and/or persistent eGFR <60 mL/min/1.73 m² and/or other evidence of kidney damage.

·         A target glycated hemoglobin (HbA1c) of ~7% is recommended to prevent or delay progression of diabetic kidney disease, including other microvascular complications of diabetes.

·         In CKD patients with diabetes, glycemic control should be a part of a multifactorial intervention strategy addressing BP and CV risk, promoting the use of angiotensin-converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARBs), statins and antiplatelet therapy where clinically indicated.

·         Sodium-glucose cotransporter-2 (SGLT2) inhibitors are being used to retard the progression of CKD in type 2 diabetes. They act by reducing plasma glucose, body weight, BP, plasma uric, acid and glomerular hyperfiltration. Few landmark trials have shown the benefits of SGLT2 inhibitors.

·         The CREDENCE trial has shown that in patients with type 2 diabetes and CKD, canagliflozin reduced the risk of kidney failure and CV events. The risk of primary outcome (doubling of serum creatinine, ESRD and death due to CV, or kidney disease) reduced by 30%, while risk of ESKD reduced by 22%.

·         In the DAPA-CKD multicenter, multinational study, dapagliflozin significantly reduced the risk of kidney failure, CV death or hospitalization for heart failure, and all-cause mortality in patients with CKD, with and without type 2 diabetes compared to placebo. It was well-tolerated in keeping with its established safety profile.

·         In patients with IgA nephropathy, when added to ACE inhibitor/ARB therapy, dapagliflozin significantly and substantially reduced the risk of CKD progression and major adverse kidney events in a prespecified analysis of DAPA-CKD trial.

·         In the EMPA-KIDNEY trial, empagliflozin therapy led to lower risk of progression of kidney disease or death from CV causes compared to placebo in patients with CKD who were at risk of disease progression. 

·         Glucagon-like peptide-1 (GLP-1) agonists such as semaglutide have also shown beneficial effects in CKD patients.

·         Start treatment with renin-angiotensin system (RAS) inhibitors (ACE inhibitors/ARBs) in patients with CKD, high BP, with or without diabetes. The highest approved should be used and gradually tailored. Changes in BP, creatinine and potassium should be monitored regularly, ideally at an interval of 2 to 4 weeks in the initial period.

·         Take measures to reduce serum potassium levels to manage the hyperkalemia associated with the use of RAS inhibitor rather than reducing the dose or stopping RAS inhibitor. 

·         Continue ACE inhibitor/ARB unless the serum creatinine rises by 30% within 4 weeks following initiation of treatment or an increase in dose. 

·         If case of symptomatic hypotension or uncontrolled hyperkalemia despite medical treatment or to reduce uremic symptoms, while treating kidney failure (eGFR <15), consider reducing the dose or stopping ACE inhibitor/ARB.

·         Mineralocorticoid receptor antagonists are effective for management of refractory hypertension but may cause hyperkalemia or a reversible decline in kidney function, especially in patients with low eGFR.

·         The 2021 KDIGO guideline recommends treatment to reduce systolic BP to <120 using standardized office BP measurement. It also recommends use of ACE inhibitors/ARBs for adults with albuminuria and high BP (systolic =120).

·         In the RENAAL trial published in NEJM, losartan reduced the primary outcome of doubling of serum creatinine, ESRD and mortality by 43% (vs. 47% with placebo) and ESRD by 19% (vs. 25% with placebo) in patients with type 2 diabetes and nephropathy. 

·         The Irbesartan Diabetic Nephropathy Trial (IDNT) also demonstrated the renoprotective effect of irbesartan in type 2 diabetic with nephropathy. Irbesartan reduced the primary composite endpoint by 20% (vs. placebo) compared to 23% reduction in risk with amlodipine.

·         In CKD patients without anemia, hemoglobin (Hb) should be measured when clinically indicated and at least annually in patients with stage 3 CKD, at least twice per year in patients with CKD4-5 ND (non-dialysis) and at least every 3 months in patients with CKD5-HD (hemodialysis) and at least every 3 months in patients with CKD5-HD and CKD5-PD (peritoneal dialysis).

·         In CKD patients with anemia not being treated with an erythropoiesis-stimulating agents (ESA), Hb should be measured when clinically indicated and at least every 3 months in patients with CKD3-5 ND and CKD5-PD and at least monthly in patients with CKD5-HD.

·         Tests in the initial evaluation of anemia included complete blood count, absolute reticulocyte count, serum ferritin, serum transferrin saturation, serum vitamin B12, and folate levels.

·         Anemia is diagnosed when Hb is <13 (in males) and <12 (in females) in adults and children older than 15 years of age.

·         In children with CKD, anemia is diagnosed when Hb is <11 in children 0.5 to 5 years, <11.5 in children 5 to 12 years, and <12 in children aged 12 to 15 years.

·         Easily correctable causes of anemia, in addition to ESA deficiency, are absolute iron deficiency, vitamin B12/folate deficiency, hypothyroidism, ACE inhibitor/ARB nonadherence. Hemoglobinopathies and bone marrow disorders are factors that are impossible to correct. 

·         In ESA hyporesponsiveness, check for adherence, reticulocyte count (if >130,000/uL, look for blood loss or hemolysis), serum vitamin B12/folate (if low, replenish), iron status (if low, replenish iron), serum parathyroid hormone (PTH) (if elevated, manage hyperparathyroidism), serum C-reactive protein (if elevated, check for and treat infection or inflammation), use of ACE inhibitor/ARB (if yes, consider reducing the dose or stopping the drug), bone marrow biopsy (manage the condition diagnosed).

·         ESA should be considered in predialysis patients with Hb levels <10 g/dL and in dialysis patients with Hb 9-10 g/dL. Target Hb for maintenance is 10-11.5 g/dL in CKD patients. 

·         Serum levels of calcium, phosphate, PTH and alkaline phosphatase (ALP) activity beginning in CKD G3a. In children, this monitoring should begin in CKD G2. 

·         In patients with CKD G3a-G5D, it is reasonable to base the frequency of monitoring serum calcium, phosphate and PTH on the presence and magnitude of abnormalities and the rate of progression
of CKD.

·         In CKD G3a-G3b: Measure serum calcium and phosphate every 6 to 12 months and for PTH based on baseline level and CKD progression.

·         In CKD G4: Measure serum calcium and phosphate every 3 to 6 months and for PTH every 6 to 12 months.

·         In CKD G5 including G5D: Measure serum calcium and phosphate every 1 to 3 months and for PTH every 3 to 6 months.

·         In CKD G4-G5D, measure ALP every 12 months or more frequently if PTH is elevated.

·         In CKD patients on treatment for CKD-MBD (mineral bone disorder) or in whom biochemical abnormalities are identified, it is reasonable to increase the frequency of measurements to monitor for trends and treatment efficacy and side effects.

·         In patients with CKD G3a-G5D, calcidiol levels can be measured. Repeat testing is done based on baseline values. 

·         Vitamin D deficiency and insufficiency should be corrected using treatment strategies recommended for the general population. Therapeutic decisions should be based on trends rather than on single lab value.

·         In patients with CKD G3a-G5D, it is reasonable to perform bone biopsy if knowledge of the type of renal osteodystrophy will impact treatment decisions. 

·         Multiple new prospective studies have documented that lower dual energy X-ray absorptiometry BMD (bone mineral density) predicts incident fractures in patients with CKD G3a-G5D.

·         CKD is closely related to CVD. Chances of having a CVD are 2.5 to 3 times higher in CKD patients; hence, they should be closely watched for CVD.

·         Reduction of cardiorenal risk in patients with CKD is through risk factor management (BP target 130/80, HbA1c <7.0, LDL lowering with statins/ezetimibe), use of ACE inhibitors/ARBs, SGLT2 inhibitors, and finerenone.

·         Calculation of GFR is very important prior to prescribing any medication. Avoid potentially nephrotoxic drugs. Metformin dose modification should be done based on GFR. 

·         CKD patients should seek medical advice before using over-the-counter medicines or nutritional protein supplements. Herbal remedies should be avoided.

·         CKD patients should be referred for specialist kidney care, in case of acute kidney injury (AKI) or abrupt sustained fall in GFR or GFR <30 mL/min/1.73 m² or consistently significant albuminuria or PER or progression of CKD or urinary red cell casts or CKD and hypertension refractory to treatment to =4 antihypertensive agents or recurrent nephrolithiasis.

·         Patients with progressive CKD in whom the risk of kidney failure within 1 year is 10% to 20% higher should be referred in time for renal replacement therapy (RRT).

·         Patients with progressive CKD should be managed in a multidisciplinary setting with access to dietary counseling, transplant options, vascular access surgery. Patient should be prepared for initiation of RRT.

·         Dialysis should be initiated when there are symptoms or signs of kidney failure, progressive deterioration in nutritional status refractory to dietary intervention or cognitive impairment.

·         Living donor renal transplantation in adults should be considered when the GFR is <20 mL/min/1.73 m² and there is evidence of progressive and irreversible CKD over the preceding 6 to 12 months.

·         CKD is a silent killer. It needs to be uncovered. CKD progression is preventable-stage the disease and treat it. 

·         Multi-risk factor intervention is critical.

·         Timely referral reduces mortality, reduces cost, and improves planning for RRT.

Participants – Member National Medical Associations: Dr Yeh Woei Chong, Singapore, Chair of Council CMAAO; Dr Angelique Coetzee, South Africa; Dr Ravi Naidu, Malaysia; Dr Wasiq Qazi, Pakistan; Dr Marthanda Pillai, India; Dr Ashraf Nizami, Pakistan; Dr Prakash Budhathoki, Nepal; Dr Mvuyisi Mzukwa, South Africa

Invitees: Dr Monica Vasudev, USA; Dr Brahm Vasudev, USA; Dr Anjali Aggarwal; Dr Colin Goldberg; Dr Manisha Kukreja; Dr S Sharma, Editor-IJCP Group

Moderator: Mr Saurabh Aggarwal