Chronic Kidney Disease Overview

Chronic Renal Failure

• Chronic renal failure (CRF) is a slow, irreversible decline in kidney function over 3 to 12 months or years. It may lead to end-stage renal failure (ESRD).
• ESRD is when renal failure is severe, and the patient needs dialysis to survive.
• The term CRF or Chronic kidney impairment has been replaced by the term Chronic Kidney Disease (CKD).
• CKD is considered kidney damage for 3 or more months.
• Damage can be detected functionally via tests like CrCL, proteinuria, or hematuria, or structurally (via kidney biopsy or radiology).

Adaptive Mechanism

• Although total kidney glomerular filtration rate (GFR) falls, remnant nephrons increase their filtration rate.
• This allows increased excretion proportionally.
• This adaptation initially blunts the drop in whole kidney GFR.
• However, it ultimately leads to glomerular hypertension and hypertrophy, and further damage.

Stages of CKD

• Stage One: Normal kidney function, urine findings suggest kidney disease. eGFR = 90 mL/min or higher
• Stage Two: Slightly reduced kidney function. eGFR = 60 to 89 mL/min
• Stage Three: Moderately reduced kidney function. eGFR= 30 to 59 mL/min
• Stage Four: Severely reduced kidney function. eGFR= 15 to 29 mL/min
• Stage Five: Very severe or end-stage kidney failure. eGFR < 15 mL/min or on dialysis.

Etiology of Chronic Renal Failure

• The most frequent causes of CRF/ESRD worldwide are diabetes and nephropathy.
• Diabetic nephropathy is more common with IDDM than NIDDM.
• Nephropathy Symptoms:
  • Persistent albuminuria (> 300 mg/24 h)
  • High blood pressure (HTN)
  • Decreased GFR
• All of these factors cause renal disease progression to ESRD.

Causes of Chronic Renal Failure/ESRD

• Glucose build-up and blood vessel damage to the kidneys causes damage overtime, leading to poor kidney filtering of waste and excess fluid. This is called persistent albuminuria or proteinuria
• High blood glucose levels create reactive oxygen species and cause oxidative stress, which results in nephropathy.
• Hyperglycemia also promotes the renin-angiotensin-aldosterone system (RAS) in the blood, which contributes to microvascular disease, altering glomerular hemodynamics and supporting diabetic nephropathy development.

Hypertension

• High blood pressure damages kidney blood vessels, affecting the ability to filter waste and fluid, causing a potential vicious cycle.
• 25-28% of ESRD patients are attributable to hypertension.

Other Causes of CKD

• Hyperlipidemia: Alone is not a significant risk factor, but with DM, it can lead to ESRD. A mechanism involving glomerular sclerosis (hardening of glomeruli) is involved.
• Primary or secondary glomerulonephritis. Inflammation of the kidney's filtering units (glomeruli).
• Chronic Tubulointerstitial nephritis: Inflammation of kidney tubule and surrounding structures.
• Polycystic kidney disease (genetic disease that causes kidney cysts to grow).
• Prolonged urinary tract obstruction (e.g., enlarged prostate, kidney stones, cancer.)
• Recurrent kidney infections (pyelonephritis).
• Vesicoureteral reflux: Urine backs up into the kidneys.
• Sickle cell nephropathy (rare).

Pre-renal Disease and CKD

• Decreased renal perfusion pressure, as from chronic heart failure or liver cirrhosis, is a pre-renal cause of chronic renal failure, resulting in a progressive loss of kidney function over time.

Intrinsic Renal Vascular Disease

• Nephrosclerosis: Chronic damage to blood vessels, glomeruli, and tubule
• Renal artery stenosis: From atherosclerosis

Post-renal Disease

• Chronic obstruction from prostatic disease, nephrolithiasis, or abdominal/pelvic tumors.
• These cause a mass effect on the ureters.

Risk Factors

• Modifiable: High blood pressure, family history of kidney disease, heart disease, abnormal kidney structure, smoking, obesity, and nephrotoxic drugs.
• Non-modifiable: Older age, male gender, being black or native American/Asian.

Prevention of CKD

• Manage existing medical conditions (diabetes, high blood pressure, heart conditions).
  • Goal for blood glucose is close to individual goals
  • Blood pressure goal is below 140/90 mmHg for people with diabetes.
• Lifestyle modifications: Healthy weight, smoking cessation, alcohol moderation, and healthy eating habits.
• Adhere to medical prescriptions.

Symptoms of CKD

• Weight loss and poor appetite
• Swelling (edema) of ankles, feet, or hands
• Shortness of breath
• Blood in the urine
• Difficulty sleeping (insomnia)
• Itchy skin
• Feeling sick
• Muscle cramps
• Headaches

Tests and Diagnosis

• Early kidney disease often lacks symptoms, so testing the kidneys function is critical.
• Testing is needed to assess the health and function of the kidneys.
• Blood tests (e.g., GFR):
  • A GFR ≥ 60mL/min/1.73m² is normal.
  • A GFR <60 may indicate kidney disease, <20 ESRD.
• Kidney function tests should be repeated 2 weeks after initial diagnosis to determine if kidney disease is acute kidney injury (AKI) or chronic kidney disease (CKD); further testing may be required over three months.

Lipid Profile

• Patients with CKD are at heightened risk for cardiovascular disease.

Renal Bone Disease

• Evidence of renal bone disease can be determined by tests like serum calcium, phosphate, 25-hydroxyvitamin D, alkaline phosphatase, and intact parathyroid hormone (PTH) levels.

Urine Test for Albumin

• Albuminuria may show some albumin in the urine. Less albuminuria is considered better.
• Urine albumin-to-creatinine ratio (UACR): 30 mg/g or less is normal; >30 may be a sign of kidney disease.

Evaluation of Chronicity

• When eGFR < 60 mL/min, pay attention to prior blood and urine testing results and clinical history to check for AKI or asymptomatic CKD.
• Clinical factors relevant to evaluation include a history of chronic hypertension, proteinuria, microhematuria, and potential for prostate disease.

Other Considerations

• Factors such as low calcium, high phosphate, or normal PTH may help differentiate acute kidney injury (AKI) from chronic kidney disease (CKD).
• BUN >140 mg/dL or creatinine >1.5 mg/dL who are relatively healthy and have normal urine flow are likely to have CKD over AKI.
• If the distinction is unclear, the kidney function tests should be repeated to determine if the decreased GFR is chronic. If so, CKD may be confirmed.

Treatment

• General Management: Adjust doses of medications for the estimated glomerular filtration rate (GFR). This is needed for proper preparation for eventual renal replacement therapy.
• Treat Reversible Causes: Identify and treat acute kidney injury causes from infection, drugs that reduce GFR, hypotension, or dehydration (vomiting, diarrhea). Avoid nephrotoxic agents such as aminoglycoside antibiotics and NSAIDS. Avoid nephrotoxic medications
• Retarding CKD Progression: Manage factors like hypertension, proteinuria, metabolic acidosis, and hyperlipidemia.
  • Smoking cessation can reduce nephrosclerosis and slow CKD progression and is an important lifestyle change.

Treating Chronic Kidney Disease

• Bicarbonate supplementation: For treating metabolic acidosis, this can help delay CKD progression.
• Intensive glucose control: In patients with diabetes, this helps delay the development of albuminuria and prevent progression to proteinuria.

Renal Replacement Therapy

• After confirming CKD progression, the patient should be offered options for renal replacement therapy (e.g., hemodialysis, peritoneal dialysis, or kidney transplantation).

Renal Transplantation

• Kidney transplantation is the best treatment option for end-stage renal disease (ESRD) and offers better long-term outcomes compared to dialysis.
• Patients are typically listed for a transplant when their eGFR is below 20 ml/min/1.73m².

Complications

• Anemia: Reduced EPO production can lead to anemia (low red blood cell count). It may result from low iron, vitamin B12, or folic acid. - Signs/symptoms include fatigue, exertion dyspnea, dizziness, headache, pallor, and decreased hematocrit -Treatment may include erythropoietin (EPO) therapy, iron supplements, or blood transfusions.
• Renal osteodystrophy and soft tissue calcification: Can result from phosphate retention affecting calcium levels.
  • Signs/symptoms include muscle spasms, mouth numbness and tingling, or itchy skin
  • Treatment options may include phosphate-binding agents, calcium supplementation, vitamin D therapy, or parathyroidectomy.
• Cardiovascular disease: Increased sodium and fluid can lead to edema, hypertension, and cardiovascular disease.
  • Signs/symptoms may include swelling of limbs (edema), high blood pressure, and fluid in the lungs.
  • These impacts need medication like diuretics (thiazides or loop diuretics).

Therapeutic Management

• Hypertension :
  • ACE inhibitors and angiotensin receptor blockers are first-line medications in patients with proteinuria.
  • Blood pressure (BP) goals in CKD patients, using KDIGO guidelines: BP <130/85 mmHg but may be lower in patients with proteinuria or diabetes.
  • Other medications, like calcium channel blockers (dihydropyridines), may be used to lower systemic vascular resistance.
• Dyslipidemia:
  • Lifestyle changes can be helpful in patients with low-to-moderate LDL cholesterol, particularly those between 100 and 129 mg/dL.
  • Statins may be a needed treatment for higher LDL values (≥130 mg/dL.
  • Treatment with lifestyle changes plus a low dose of statin may be used when triglycerides are very high (>200 mg/dL).
• Metabolic acidosis:
  • Sodium bicarbonate can be beneficial in treating metabolic acidosis to help replenish bicarbonate stores found within the body. This also helps to prevent complications.

This quiz explores essential concepts related to chronic kidney disease (CKD), including its definition, causes, and diagnostic features. Test your knowledge on the changes and challenges that arise from CKD, particularly in the context of diabetic nephropathy and renal function. Enhance your understanding of the adaptive mechanisms and potential complications associated with kidney health.