End-Stage Renal Disease: A Comprehensive Guide to Diagnosis and Management

Introduction

End-stage renal disease (ESRD), also known as kidney failure, affects over 500,000 individuals in the United States, marking a critical stage in the progression of chronic kidney disease (CKD). This terminal condition significantly diminishes life quality and increases mortality rates. Chronic Kidney Disease (CKD) is characterized by markers of kidney damage, notably proteinuria and reduced glomerular filtration rate (GFR), as defined by the Kidney Disease Improving Global Outcomes (KDIGO) guidelines. Diabetes mellitus stands out as a primary cause of ESRD globally. Accurate and timely Diagnosis Of Esrd is crucial for effective management and improving patient outcomes. This article delves into the essential aspects of ESRD, providing a detailed guide for healthcare professionals on its diagnosis, evaluation, and management strategies. Furthermore, it emphasizes the collaborative role of an interprofessional team in optimizing patient care for individuals with ESRD.

Chronic kidney disease is a severe condition necessitating vigilant monitoring for disease progression and prompt referral to specialists for interventions like dialysis or kidney transplantation. KDIGO guidelines define CKD based on kidney damage markers, specifically proteinuria and glomerular filtration rate. CKD is diagnosed when GFR is below 60 mL/min and albumin levels exceed 30 mg per gram of creatinine, alongside structural or functional kidney abnormalities lasting over three months. End-stage renal disease is clinically defined by a GFR of less than 15 mL/min.

The KDIGO 2012 clinical practice guideline classifies CKD into five stages based on GFR levels, providing a structured approach to understanding disease severity:

• Stage 1: Kidney damage with normal GFR (≥ 90 mL/min)
• Stage 2: Mildly reduced GFR (60-89 mL/min)
• Stage 3a: Moderately reduced GFR (45-59 mL/min)
• Stage 3b: Moderately reduced GFR (30-44 mL/min)
• Stage 4: Severely reduced GFR (15-29 mL/min)
• Stage 5: Kidney failure (GFR < 15 mL/min), indicative of End-Stage Renal Disease

Etiology of ESRD

End-stage renal disease is the culmination of various chronic conditions that impair kidney function over time. Diabetes mellitus is the most prevalent cause of ESRD in both developed and developing nations. Beyond diabetes, other significant etiologies include:

• Hypertension: Prolonged high blood pressure can damage the delicate blood vessels in the kidneys.
• Vascular Diseases: Conditions like renal artery stenosis can reduce blood flow to the kidneys, leading to damage.
• Glomerular Diseases: Primary or secondary glomerular diseases, such as glomerulonephritis, directly affect the kidney’s filtering units.
• Cystic Kidney Diseases: Polycystic kidney disease, characterized by cyst formation in the kidneys, progressively impairs renal function.
• Tubulointerstitial Diseases: Conditions affecting the tubules and interstitial spaces of the kidneys, such as chronic pyelonephritis and tubulointerstitial nephritis.
• Urinary Tract Obstruction or Dysfunction: Blockages or functional issues in the urinary tract can cause backpressure and kidney damage.
• Recurrent Kidney Stone Disease: Frequent kidney stone formation can lead to chronic kidney injury.
• Congenital Kidney or Bladder Defects: Birth defects affecting kidney structure or function can predispose individuals to ESRD.
• Unrecovered Acute Kidney Injury (AKI): Failure to fully recover from AKI can lead to chronic kidney disease and eventually ESRD.
• Medications: Certain drugs, including non-steroidal anti-inflammatory drugs (NSAIDs), calcineurin inhibitors, and antiretrovirals, can be nephrotoxic and contribute to ESRD development.

Epidemiology of End-Stage Renal Disease

The incidence and prevalence of ESRD represent a growing global health concern. According to the United States Renal Data System (USRDS), in 2015, there were 124,411 new ESRD diagnoses in the US, indicating an increasing burden of kidney failure. The prevalence has been steadily rising by approximately 20,000 cases annually. Kidney disease ranks as the ninth leading cause of death in the United States, highlighting its significant impact on public health.

Racial and Ethnic Disparities:

Significant racial and ethnic disparities exist in the prevalence of ESRD. In 2015, African Americans experienced ESRD rates three times higher than Whites (393.5 versus 139.9 per million population). American Indians or Alaska Natives showed approximately ten times higher prevalence, and Native Hawaiians or Pacific Islanders had twice as high prevalence rates compared to Whites. Asian Americans also had a 1.3 times higher prevalence. However, it’s noteworthy that incidence rates among African Americans have been decreasing since 2006, with an overall reduction of 21%, and a more pronounced decrease observed in American Indians/Alaska Natives.

Age and ESRD:

The prevalence of CKD, which precedes ESRD, significantly increases with age. The most rapid increase is observed in individuals aged 60 years and older. For instance, prevalence rates are around 6.0% in the 18 to 44 age group, escalating to 38.1% in those over 65 years. This age-related increase underscores the importance of monitoring kidney function in older populations.

Sex Differences:

Cumulative incidence of end-stage renal disease is observed to be higher in males compared to females, suggesting a potential gender-based susceptibility or risk factor profile.

Pathophysiology of ESRD

The pathophysiology of ESRD is a complex process involving progressive nephron damage and adaptive mechanisms that eventually fail. Each nephron in a healthy kidney contributes to the overall glomerular filtration rate (GFR). Initially, the decline in kidney function may be asymptomatic. The progression of renal failure depends on the underlying cause, but a common feature is the activation of homeostatic mechanisms, including hyperfiltration of the remaining nephrons.

The kidneys attempt to maintain GFR despite nephron loss through hyperfiltration and compensatory hypertrophy of the surviving nephrons. This adaptation allows for continued clearance of plasma solutes, masking the early stages of renal impairment as creatinine levels may remain within the normal range. For example, an increase in plasma creatinine from 0.6 mg/dL to 1.2 mg/dL, although still within the normal range, actually indicates a 50% reduction in functioning nephron mass.

However, this adaptive mechanism is not sustainable and contributes to further glomerular damage. Increased glomerular capillary pressure from hyperfiltration can injure the capillaries, leading to focal and segmental glomerulosclerosis (FSGS) and eventually global glomerulosclerosis. At this stage, interventions like ACE inhibitors or ARBs become crucial to slow disease progression and preserve renal function by managing intraglomerular pressure.

Several factors can exacerbate renal injury in CKD:

• Nephrotoxins: Exposure to substances toxic to the kidneys, such as NSAIDs.
• Systemic Hypertension: Uncontrolled high blood pressure.
• Proteinuria: Elevated protein levels in urine, indicating glomerular damage.
• Dehydration: Reduced fluid volume can stress kidney function.
• Smoking: A known risk factor for kidney disease progression.
• Hyperlipidemia: High levels of lipids in the blood.
• Uncontrolled Diabetes: Poor glycemic control accelerates kidney damage in diabetic nephropathy.
• Hyperphosphatemia: Elevated phosphate levels, common in later CKD stages.

Key Physiological Derangements in ESRD:

• Hyperkalemia: Potassium excretion is maintained in early CKD, but as GFR drops below 20-25 mL/min/1.73 m², the kidneys’ ability to excrete potassium diminishes, leading to hyperkalemia.
• Metabolic Acidosis: Stage 5 CKD typically presents with high anion gap metabolic acidosis. This occurs due to reduced ammonia production in proximal tubules, impairing acid excretion. Accumulation of phosphates, sulfates, and organic anions contributes to the increased anion gap. Metabolic acidosis has detrimental effects on protein balance, leading to negative nitrogen balance, increased protein degradation, reduced albumin synthesis, and bone mineral loss.
• Salt and Water Handling Abnormalities: Volume overload becomes common as GFR falls below 10-15 mL/min/1.73 m², resulting from impaired sodium and water excretion. This leads to edema, pulmonary edema, and hypertension. Conversely, tubulointerstitial diseases might cause polyuria and volume depletion due to impaired urine concentration.
• Anemia: Normochromic normocytic anemia develops due to decreased renal synthesis of erythropoietin. Other contributing factors include chronic blood loss from uremia-induced platelet dysfunction, secondary hyperparathyroidism, inflammation, and nutritional deficiencies.
• Bone Disease (Renal Osteodystrophy): Renal bone disease is a frequent complication, encompassing high-turnover bone disease from hyperparathyroidism, low-turnover bone disease (adynamic bone disease), defective mineralization (osteomalacia), mixed disease, and beta-2-microglobulin–associated bone disease. Secondary hyperparathyroidism is driven by hyperphosphatemia, hypocalcemia, decreased calcitriol synthesis, and parathyroid gland alterations.

History and Physical Examination in ESRD Diagnosis

Diagnosis of ESRD often involves recognizing a constellation of clinical signs and symptoms. Patients may present with:

• Volume overload unresponsive to diuretics
• Hypertension resistant to multiple medications
• Anemia and related fatigue
• Mineral and bone disorders
• Metabolic disturbances including hyperkalemia, hyponatremia, metabolic acidosis, and hypo/hypercalcemia.

Metabolic acidosis in stage 5 CKD contributes to protein-energy malnutrition, muscle weakness, and loss of lean body mass. Salt and water retention manifest as peripheral edema, pulmonary edema, and hypertension. Anemia leads to fatigue, cognitive impairment, and reduced quality of life, potentially progressing to heart failure.

Uremic symptoms, indicative of ESRD, include:

• Pericarditis
• Encephalopathy
• Peripheral neuropathy
• Restless leg syndrome
• Anorexia, nausea, vomiting, diarrhea
• Dry skin, pruritus, ecchymosis
• Malnutrition
• Erectile dysfunction, decreased libido, amenorrhea
• Platelet dysfunction

Uremic toxicity signifies the urgent need for dialysis. ESRD symptoms typically become prominent in stages 4 and 5 when GFR is below 30 ml/min. However, some patients with nephrotic syndrome or cystic renal disease may present earlier. Depression is prevalent in ESRD patients and should be routinely screened for.

Evaluation and Diagnosis of ESRD

Diagnosis of chronic kidney disease, and subsequently ESRD, relies on evidence of kidney damage present for at least three months, or a GFR below 60 mL/min for the same duration.

GFR Estimation:

Glomerular filtration rate is estimated using equations like MDRD (Modification of Diet in Renal Disease Study), CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration), and Cockcroft-Gault formula. The CKD-EPI equation is generally considered the most accurate, adjusting for age, race, and gender, though it may underestimate GFR above 60 mL/min.

Further Diagnostic Evaluations:

• Complete Blood Count (CBC): Typically reveals normochromic normocytic anemia.
• Basic Metabolic Panel (BMP): Shows elevated BUN and serum creatinine, often with hyperkalemia or low bicarbonate. Serum albumin may be low. Phosphate, 25-hydroxyvitamin D, alkaline phosphatase, and PTH levels are assessed for renal bone disease. A lipid profile is important due to increased cardiovascular risk.
• Urinalysis: Spot urine protein/creatinine ratio quantifies albuminuria. Values above 30 mg/g are abnormal, and over 300 mg/g indicate severely impaired renal function. 24-hour urine protein can also be measured, with values exceeding 3.5 g concerning for nephrotic range proteinuria.
• Renal Ultrasonography: Used to assess kidney structure, identify hydronephrosis, and detect abnormalities like polycystic kidneys. In advanced renal failure, kidneys may appear small and echogenic, while in diabetic nephropathy, they might be of normal size. Ultrasound helps estimate size, identify obstructions, stones, echogenicity, and cortical thinning.

Advanced Radiological and Specific Tests:

• Radiology: Plain abdominal radiography can detect radio-opaque stones or nephrocalcinosis. Voiding cystourethrogram (VCUG) diagnoses vesicoureteral reflux. CT scans provide detailed imaging of renal masses and cysts and are sensitive for stone detection. MRA accurately diagnoses renal artery stenosis. Renal radionuclide scans with captopril can also diagnose renal artery stenosis and quantify differential renal GFR contribution.
• Renal Biopsy: Percutaneous ultrasound-guided renal biopsy is indicated when the diagnosis remains unclear after initial workup.
• Specific Blood and Urine Tests: Serum and urine protein electrophoresis for multiple myeloma, ANA and anti-dsDNA for SLE, serum complement levels, C-ANCA and P-ANCA for vasculitides, anti-GBM antibodies for Goodpasture syndrome, and serology for Hepatitis B/C, HIV, and VDRL may be ordered based on clinical suspicion.

Treatment and Management of ESRD

Treatment of end-stage renal disease is multifaceted, aiming to address immediate complications and slow disease progression while planning for renal replacement therapy.

Conservative Management:

• Treating Underlying Causes and Managing Comorbidities: This includes strict blood pressure control (target <130/80 mmHg), especially in patients with diabetes or proteinuria (>30 mg/24 hours). ACE inhibitors or ARBs are recommended for proteinuria management, particularly when initiated early in CKD.
• Glycemic Control: Maintaining HbA1c <7% is crucial for diabetic patients to prevent microvascular complications. SGLT-2 inhibitors may offer renal protection in type 2 diabetes.
• Metabolic Acidosis Correction: Supplemental renal bicarbonate may slow ESRD progression.
• Dyslipidemia Management: Statins are used to manage hypertriglyceridemia and reduce cardiovascular risk.

Symptomatic Treatment:

• Volume Overload/Pulmonary Edema: Loop diuretics or ultrafiltration are used to manage fluid overload.
• Uremic Manifestations: Long-term renal replacement therapy (hemodialysis, peritoneal dialysis, or kidney transplantation) is required.
• Anemia: Erythropoiesis-stimulating agents (ESAs) like erythropoietin are used to treat anemia.
• Hyperphosphatemia: Phosphate binders (calcium acetate, sevelamer carbonate, lanthanum carbonate) and dietary phosphate restriction are essential.
• Hypocalcemia: Monitored and treated with vitamin D supplementation. Ergocalciferol followed by cholecalciferol may be prescribed.
• Hyperparathyroidism: Treated with calcitriol, vitamin D analogs, or calcimimetics.

Lifestyle and Dietary Modifications:

• Low salt diet (<2 g/day)
• Renal diet (low phosphorus foods)
• Protein restriction (0.8 g/kg body weight/day)
• Smoking cessation

Renal Replacement Therapy Planning:

Early education about disease progression, dialysis modalities, and kidney transplantation is crucial. Preemptive arteriovenous fistula creation should be considered for patients likely needing hemodialysis. Timely referral for renal transplantation is essential for all eligible ESRD patients.

Indications for Renal Replacement Therapy:

• Severe metabolic acidosis
• Hyperkalemia
• Pericarditis
• Encephalopathy
• Intractable volume overload
• Failure to thrive and malnutrition
• Peripheral neuropathy
• Intractable gastrointestinal symptoms
• GFR of 5 to 9 mL/min/1.73 m^2, regardless of symptoms.

Differential Diagnosis of ESRD

The clinical presentation of end-stage renal disease can overlap with various other disorders, and many diseases can lead to ESRD. Therefore, when considering the diagnosis of ESRD, it’s important to consider the following differential diagnoses:

• Chronic glomerulonephritis
• Chronic pyelonephritis
• Rapidly progressive glomerulonephritis
• Nephropathy of pregnancy/pregnancy toxemia
• Unclassifiable nephritis
• Polycystic kidney disease
• Nephrosclerosis
• Malignant hypertension
• Diabetic nephropathy
• Systemic lupus erythematosus nephritis
• Amyloid kidney
• Gouty kidney
• Renal failure due to congenital metabolic abnormalities
• Renal/urinary tract tuberculosis
• Renal/urinary tract calculus
• Renal/urinary tract tumor
• Obstructive urinary tract disease
• Myeloma
• Renal hypoplasia

Prognosis of ESRD

End-stage renal disease is a progressive and life-limiting condition. Renal replacement therapy is essential to prevent mortality. ESRD is associated with frequent hospitalizations, high healthcare costs, and significant metabolic disturbances. Mortality rates are substantially higher in ESRD patients compared to the general population. Even with dialysis, mortality ranges from 20% to 50% over 24 months. Hyperkalemia and adverse cardiac events are leading causes of death. Mortality is higher in men and African Americans. The highest mortality risk is within the first six months of dialysis initiation. The 5-year survival rate for dialysis patients in the US is approximately 35%, and lower at around 25% for diabetic patients. In children with ESRD, puberty may be delayed, and vitamin D deficiency is common, increasing mortality risk.

Complications of ESRD

Complications of end-stage renal disease are broadly categorized into those arising from ESRD itself and those related to vascular access or dialysis.

ESRD-Related Complications:

• Coronary Heart Disease: The leading cause of death in ESRD patients, with a 10 to 30 times higher cardiovascular mortality risk than the general population.
• Peripheral Vascular Disease
• Hypertension
• Mineral and Bone Disorders: Secondary to hyperparathyroidism and vitamin D deficiency.
• Hyperuricemia
• Metabolic Acidosis
• Hyperphosphatemia
• Hypoalbuminemia
• Anemia
• Decreased Libido and Erectile Dysfunction

Vascular Access/Dialysis-Related Complications:

• Bleeding
• Local or disseminated intravascular infection
• Graft occlusion
• Electrolyte abnormalities post-dialysis
• Dialysis dementia
• Dialysis disequilibrium syndrome

Consultations in ESRD Management

Effective management of end-stage renal disease requires a multidisciplinary interprofessional healthcare team, including:

• Nephrologist: Leads the overall renal care and dialysis/transplant planning.
• Intensivist: Manages acute complications, especially in hospitalized patients.
• Renal Transplant Surgeon: Evaluates and performs kidney transplants.
• Nurse Educator: Provides patient education on disease management, dialysis, and lifestyle modifications.
• Pharmacist: Manages medications, optimizes drug regimens, and advises on nephrotoxic drug avoidance.
• Nutritionist: Develops and monitors renal-specific dietary plans.

Deterrence and Patient Education for ESRD

The U.S. Preventive Services Task Force (USPSTF) does not recommend general screening for CKD in asymptomatic individuals. However, targeted screening for high-risk groups, such as those with diabetes or hypertension, is recommended, primarily through proteinuria testing. It’s important to note that proteinuria screening may not be necessary for patients already on ACEI or ARB therapy.

Patient education for individuals with end-stage renal disease is critical and should include:

• Avoidance of nephrotoxic drugs, particularly NSAIDs.
• Comprehensive counseling on renal replacement modalities (peritoneal dialysis, hemodialysis, transplantation).
• Importance of timely vascular access placement for hemodialysis.
• Risks associated with pregnancy in ESRD.
• Dietary phosphate restriction.
• Potassium restriction in diet.
• Sodium and water restriction to manage volume overload.
• Protein restriction to alleviate uremic symptoms.
• Benefits of reduced salt intake in slowing diabetic CKD progression.

Pearls and Key Considerations in ESRD

• End-stage renal disease is defined by a GFR less than 15 mL/min and is a terminal condition.
• Diabetic nephropathy and hypertension are the leading causes of ESRD in the US.
• Other etiologies include glomerulonephritis, cystic kidney disease, chronic infections, and obstructions.
• Clinical presentation can be diverse, including nausea, vomiting, metabolic and electrolyte imbalances, hematologic derangements, seizures, coma, bleeding, fluid overload, refractory hypertension, and uremic pericarditis.
• Vigilant monitoring of GFR and proteinuria in at-risk populations is crucial for managing CKD progression.
• Early specialist referral is essential for timely dialysis or transplant planning.

Enhancing Healthcare Team Outcomes in ESRD

Managing end-stage renal disease effectively requires a coordinated interprofessional team approach to improve patient outcomes and reduce healthcare costs. Given the lack of a cure and the short-term nature of current treatments, preventing disease progression is paramount.

An optimal interprofessional team should include a nurse educator, specialized pharmacist, nutritionist, social worker, primary care provider, and nephrologist. The nurse educator plays a vital role in patient education, particularly regarding lifestyle modifications and protecting vascular access sites. Pharmacists are crucial for medication management, preventing nephrotoxic drug use, and guiding providers on appropriate drug choices. Nutritionists provide tailored dietary plans, and social workers ensure patients have adequate support and resources. Collaborative communication and accurate record-keeping among team members are essential for delivering optimal care and improving outcomes for ESRD patients.

Review Questions

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References

1.Jin DC, Yun SR, Lee SW, Han SW, Kim W, Park J, Kim YK. Lessons from 30 years’ data of Korean end-stage renal disease registry, 1985-2015. Kidney Res Clin Pract. 2015 Sep;34(3):132-9.

2.Scott IA, Scuffham P, Gupta D, Harch TM, Borchi J, Richards B. Going digital: a narrative overview of the effects, quality and utility of mobile apps in chronic disease self-management. Aust Health Rev. 2020 Feb;44(1):62-82.

3.Sgambat K, Cheng YI, Charnaya O, Moudgil A. The prevalence and outcome of children with failure to thrive after pediatric kidney transplantation. Pediatr Transplant. 2019 Feb;23(1):e13321.

4.Acosta-Ochoa I, Bustamante-Munguira J, Mendiluce-Herrero A, Bustamante-Bustamante J, Coca-Rojo A. Impact on Outcomes across KDIGO-2012 AKI Criteria According to Baseline Renal Function. J Clin Med. 2019 Aug 28;8(9)

5.Ghaderian SB, Hayati F, Shayanpour S, Beladi Mousavi SS. Diabetes and end-stage renal disease; a review article on new concepts. J Renal Inj Prev. 2015;4(2):28-33.

6.Goksu SY, Leslie SW, Khattar D. StatPearls [Internet]. StatPearls Publishing; Treasure Island (FL): Oct 23, 2023. Renal Cystic Disease.

7.Clements JM, Rosca M, Cavallin C, Falkenhagen S, Ittoop T, Jung CK, Mazzella M, Reed JA, Schluentz M, VanDyke C. Type 2 Diabetes and Chronic Conditions Disparities in Medicare Beneficiaries in the State of Michigan. Am J Med Sci. 2020 Apr;359(4):218-225.

8.Joyce E, Glasner P, Ranganathan S, Swiatecka-Urban A. Tubulointerstitial nephritis: diagnosis, treatment, and monitoring. Pediatr Nephrol. 2017 Apr;32(4):577-587.

9.Shoag J, Halpern J, Goldfarb DS, Eisner BH. Risk of chronic and end stage kidney disease in patients with nephrolithiasis. J Urol. 2014 Nov;192(5):1440-5.

10.Chang YK, Liu JS, Hsu YH, Tarng DC, Hsu CC. Increased Risk of End-Stage Renal Disease (ESRD) Requiring Chronic Dialysis is Associated With Use of Nonsteroidal Anti-Inflammatory Drugs (NSAIDs): Nationwide Case-Crossover Study. Medicine (Baltimore). 2015 Sep;94(38):e1362.

11.Yu TM, Sun CS, Lin CL, Wang CY, Chang PY, Chou CY, Chuang YW, Lee BJ, Kao CH. Risk factors associated with end-stage renal disease (ESRD) in patients with atherosclerotic renal artery stenosis: a nationwide population-based analysis. Medicine (Baltimore). 2015 May;94(21):e912.

12.Kruegel J, Rubel D, Gross O. Alport syndrome–insights from basic and clinical research. Nat Rev Nephrol. 2013 Mar;9(3):170-8.

13.Chen S, Chen H, Liu Z, Zhang H, Hu W, Tang Z, Liu Z. Pathological spectrums and renal prognosis of severe lupus patients with rapidly progressive glomerulonephritis. Rheumatol Int. 2015 Apr;35(4):709-17.

14.Maroz N, Segal MS. Lupus nephritis and end-stage kidney disease. Am J Med Sci. 2013 Oct;346(4):319-23.

15.Sexton DJ, Reule S, Foley RN. End-Stage Kidney Disease From Scleroderma in the United States, 1996 to 2012. Kidney Int Rep. 2018 Jan;3(1):148-154.

16.Abraham AG, Althoff KN, Jing Y, Estrella MM, Kitahata MM, Wester CW, Bosch RJ, Crane H, Eron J, Gill MJ, Horberg MA, Justice AC, Klein M, Mayor AM, Moore RD, Palella FJ, Parikh CR, Silverberg MJ, Golub ET, Jacobson LP, Napravnik S, Lucas GM., North American AIDS Cohort Collaboration on Research and Design (NA-ACCORD) of the International Epidemiologic Databases to Evaluate AIDS (IeDEA). End-stage renal disease among HIV-infected adults in North America. Clin Infect Dis. 2015 Mar 15;60(6):941-9.

17.Tang W, McDonald SP, Hawley CM, Badve SV, Boudville N, Brown FG, Clayton PA, Campbell SB, de Zoysa JR, Johnson DW. End-stage renal failure due to amyloidosis: outcomes in 490 ANZDATA registry cases. Nephrol Dial Transplant. 2013 Feb;28(2):455-61.

18.Evans RD, Laing CM, Ciurtin C, Walsh SB. Tubulointerstitial nephritis in primary Sjögren syndrome: clinical manifestations and response to treatment. BMC Musculoskelet Disord. 2016 Jan 05;17:2.

19.Matthesen AT, Thaarup J, Hagstrøm S, Matthesen KT, Thorsteinsson K. [Tubulointerstitial nephritis and uveitis syndrome]. Ugeskr Laeger. 2022 Mar 21;184(12)

20.Moriconi D, Giannese D, Capecchi R, Cupisti A, Barsotti S, Morganti R, Orsitto E, Gaetano Tavoni A, Francesca Egidi M. Risk factors for relapse and long-term outcome of idiopathic retroperitoneal fibrosis. Clin Exp Nephrol. 2019 Sep;23(9):1147-1153.

21.Harding JL, Pavkov ME, Magliano DJ, Shaw JE, Gregg EW. Global trends in diabetes complications: a review of current evidence. Diabetologia. 2019 Jan;62(1):3-16.

22.Ishigami J, Matsushita K. Clinical epidemiology of infectious disease among patients with chronic kidney disease. Clin Exp Nephrol. 2019 Apr;23(4):437-447.

23.Wyld MLR, Morton RL, Aouad L, Magliano D, Polkinghorne KR, Chadban S. The impact of comorbid chronic kidney disease and diabetes on health-related quality-of-life: a 12-year community cohort study. Nephrol Dial Transplant. 2021 May 27;36(6):1048-1056.

24.Lees JS, Welsh CE, Celis-Morales CA, Mackay D, Lewsey J, Gray SR, Lyall DM, Cleland JG, Gill JMR, Jhund PS, Pell J, Sattar N, Welsh P, Mark PB. Glomerular filtration rate by differing measures, albuminuria and prediction of cardiovascular disease, mortality and end-stage kidney disease. Nat Med. 2019 Nov;25(11):1753-1760.

25.Schnaper HW. Remnant nephron physiology and the progression of chronic kidney disease. Pediatr Nephrol. 2014 Feb;29(2):193-202.

26.Xia J, Wang L, Ma Z, Zhong L, Wang Y, Gao Y, He L, Su X. Cigarette smoking and chronic kidney disease in the general population: a systematic review and meta-analysis of prospective cohort studies. Nephrol Dial Transplant. 2017 Mar 01;32(3):475-487.

27.Gilligan S, Raphael KL. Hyperkalemia and Hypokalemia in CKD: Prevalence, Risk Factors, and Clinical Outcomes. Adv Chronic Kidney Dis. 2017 Sep;24(5):315-318.

28.Kraut JA, Madias NE. Metabolic Acidosis of CKD: An Update. Am J Kidney Dis. 2016 Feb;67(2):307-17.

29.Raghavan R, Eknoyan G. Acute interstitial nephritis – a reappraisal and update. Clin Nephrol. 2014 Sep;82(3):149-62.

30.Atkinson MA, Warady BA. Anemia in chronic kidney disease. Pediatr Nephrol. 2018 Feb;33(2):227-238.

31.Bover J, Ureña P, Brandenburg V, Goldsmith D, Ruiz C, DaSilva I, Bosch RJ. Adynamic bone disease: from bone to vessels in chronic kidney disease. Semin Nephrol. 2014 Nov;34(6):626-40.

32.Rodríguez-Ortiz ME, Rodríguez M. Recent advances in understanding and managing secondary hyperparathyroidism in chronic kidney disease. F1000Res. 2020;9

33.Ni X, Zhang J, Zhang P, Wu F, Xia M, Ying G, Chen J. Effects of spironolactone on dialysis patients with refractory hypertension: a randomized controlled study. J Clin Hypertens (Greenwich). 2014 Sep;16(9):658-63.

34.Whitney DG, Schmidt M, Bell S, Morgenstern H, Hirth RA. Incidence Rate of Advanced Chronic Kidney Disease Among Privately Insured Adults with Neurodevelopmental Disabilities. Clin Epidemiol. 2020;12:235-243.

35.Natale P, Palmer SC, Ruospo M, Saglimbene VM, Rabindranath KS, Strippoli GF. Psychosocial interventions for preventing and treating depression in dialysis patients. Cochrane Database Syst Rev. 2019 Dec 02;12(12):CD004542.

36.Kyte D, Bishop J, Brettell E, Calvert M, Cockwell P, Dutton M, Eddington H, Hadley G, Ives NJ, Jackson LJ, Stringer S, Valente M. Use of an electronic patient-reported outcome measure in the management of patients with advanced chronic kidney disease: the RePROM pilot trial protocol. BMJ Open. 2018 Oct 28;8(10):e026080.

37.Weckmann GFC, Stracke S, Haase A, Spallek J, Ludwig F, Angelow A, Emmelkamp JM, Mahner M, Chenot JF. Diagnosis and management of non-dialysis chronic kidney disease in ambulatory care: a systematic review of clinical practice guidelines. BMC Nephrol. 2018 Oct 11;19(1):258.

38.Jonsson A, Viklund I, Jonsson A, Valham F, Bergdahl E, Lindmark K, Norberg H. Comparison of creatinine-based methods for estimating glomerular filtration rate in patients with heart failure. ESC Heart Fail. 2020 Jun;7(3):1150-1160.

39.Elgari MM, Khabour OF, Elhag HAEH, Muddathir ARM. Hematological indices of end-stage chronic renal failure patients in Sudan: With or without iron supplements. Pak J Pharm Sci. 2019 Mar;32(2 (Supplementary)):765-768.

40.Damasiewicz MJ, Nickolas TL. Rethinking Bone Disease in Kidney Disease. JBMR Plus. 2018 Nov;2(6):309-322.

41.Petrucci I, Clementi A, Sessa C, Torrisi I, Meola M. Ultrasound and color Doppler applications in chronic kidney disease. J Nephrol. 2018 Dec;31(6):863-879.

42.Eroglu Y, Yildirim K, Çinar A, Yildirim M. Diagnosis and grading of vesicoureteral reflux on voiding cystourethrography images in children using a deep hybrid model. Comput Methods Programs Biomed. 2021 Oct;210:106369.

43.Wu Y, Zhang J, Wang Y, Wang T, Han Q, Guo R, Zhang R, Ren H, Zhu Y, Xu H, Li L, Tong N, Liu F. The association of hematuria on kidney clinicopathologic features and renal outcome in patients with diabetic nephropathy: a biopsy-based study. J Endocrinol Invest. 2020 Sep;43(9):1213-1220.

44.Manley HJ, Aweh G, Weiner DE, Jiang H, Miskulin DC, Johnson D, Lacson EK. Multidisciplinary Medication Therapy Management and Hospital Readmission in Patients Undergoing Maintenance Dialysis: A Retrospective Cohort Study. Am J Kidney Dis. 2020 Jul;76(1):13-21.

45.Son HE, Ryu JY, Go S, Yi Y, Kim K, Oh YK, Oh KH, Chin HJ. Association of ambulatory blood pressure monitoring with renal outcome in patients with chronic kidney disease. Kidney Res Clin Pract. 2020 Mar 31;39(1):70-80.

46.Weir MR, McCullough PA, Buse JB, Anderson J. Renal and Cardiovascular Effects of Sodium Glucose Co-Transporter 2 Inhibitors in Patients with Type 2 Diabetes and Chronic Kidney Disease: Perspectives on the Canagliflozin and Renal Events in Diabetes with Established Nephropathy Clinical Evaluation Trial Results. Am J Nephrol. 2020;51(4):276-288.

47.Tanemoto M. Progression of Metabolic Acidosis in Chronic Kidney Disease. Kidney Dis (Basel). 2020 Jan;6(1):59-63.

48.Jung J, Bae GH, Kang M, Kim SW, Lee DH. Statins and All-Cause Mortality in Patients Undergoing Hemodialysis. J Am Heart Assoc. 2020 Mar 03;9(5):e014840.

49.Zand L, Kumar R. The Use of Vitamin D Metabolites and Analogues in the Treatment of Chronic Kidney Disease. Endocrinol Metab Clin North Am. 2017 Dec;46(4):983-1007.

50.Dixon BS. Timing of arteriovenous fistula placement: keeping it in perspective. J Am Soc Nephrol. 2015 Feb;26(2):241-3.

51.Perrone RD, Mouksassi MS, Romero K, Czerwiec FS, Chapman AB, Gitomer BY, Torres VE, Miskulin DC, Broadbent S, Marier JF. Total Kidney Volume Is a Prognostic Biomarker of Renal Function Decline and Progression to End-Stage Renal Disease in Patients With Autosomal Dominant Polycystic Kidney Disease. Kidney Int Rep. 2017 May;2(3):442-450.

52.Gurung R, Li T. Renal Amyloidosis: Presentation, Diagnosis, and Management. Am J Med. 2022 Apr;135 Suppl 1:S38-S43.

53.Yang CW, Harris DCH, Luyckx VA, Nangaku M, Hou FF, Garcia Garcia G, Abu-Aisha H, Niang A, Sola L, Bunnag S, Eiam-Ong S, Tungsanga K, Richards M, Richards N, Goh BL, Dreyer G, Evans R, Mzingajira H, Twahir A, McCulloch MI, Ahn C, Osafo C, Hsu HH, Barnieh L, Donner JA, Tonelli M. Global case studies for chronic kidney disease/end-stage kidney disease care. Kidney Int Suppl (2011). 2020 Mar;10(1):e24-e48.

54.Verghese PS. Pediatric kidney transplantation: a historical review. Pediatr Res. 2017 Jan;81(1-2):259-264.

55.Fujii H, Kono K, Nishi S. Characteristics of coronary artery disease in chronic kidney disease. Clin Exp Nephrol. 2019 Jun;23(6):725-732.

56.Matsushita K, Ballew SH, Coresh J, Arima H, Ärnlöv J, Cirillo M, Ebert N, Hiramoto JS, Kimm H, Shlipak MG, Visseren FLJ, Gansevoort RT, Kovesdy CP, Shalev V, Woodward M, Kronenberg F., Chronic Kidney Disease Prognosis Consortium. Measures of chronic kidney disease and risk of incident peripheral artery disease: a collaborative meta-analysis of individual participant data. Lancet Diabetes Endocrinol. 2017 Sep;5(9):718-728.

57.Fink HA, Ishani A, Taylor BC, Greer NL, MacDonald R, Rossini D, Sadiq S, Lankireddy S, Kane RL, Wilt TJ. Screening for, monitoring, and treatment of chronic kidney disease stages 1 to 3: a systematic review for the U.S. Preventive Services Task Force and for an American College of Physicians Clinical Practice Guideline. Ann Intern Med. 2012 Apr 17;156(8):570-81.

58.Waheed AA, Pedraza F, Lenz O, Isakova T. Phosphate control in end-stage renal disease: barriers and opportunities. Nephrol Dial Transplant. 2013 Dec;28(12):2961-8.

59.D’Alessandro C, Rossi A, Innocenti M, Ricchiuti G, Bozzoli L, Sbragia G, Meola M, Cupisti A. Dietary protein restriction for renal patients: don’t forget protein-free foods. J Ren Nutr. 2013 Sep;23(5):367-71.

60.Anderson CAM, Nguyen HA. Nutrition education in the care of patients with chronic kidney disease and end-stage renal disease. Semin Dial. 2018 Mar;31(2):115-121.

Disclosures: Muhammad Hashmi, Onecia Benjamin, and Sarah Lappin declare no relevant financial relationships with ineligible companies.