Table 1.

Details the laboratory abnormalities and diagnosis of chronic kidney disease.

Laboratory abnormalities: The kidneys primarily maintain homeostasis through their fundamental functions of filtration, reabsorption, and secretion. It plays a vital role in the regulation of extracellular fluid volume, serum osmolality, and electrolyte concentrations, excretion of waste products and toxins such as urea, creatinine, and uric acid, as well as the production of hormones, e.g., erythropoietin and 1,25 dihydroxy vitamin D and renin.[16] CKD results in the derangement of the homeostatic mechanisms of the kidneys, which leads to fluid and electrolyte disturbance, endocrine and metabolic disorders, and hematological abnormalities. Consequently, the laboratory abnormalities in CKD include impaired glomerular filtration propagated by the Renin-Angiotensin System (RAS) activation, which clinically manifests as proteinuria.[17] Fluid and electrolyte disturbances result in hyponatremia, hyperkalemia, hypervolemia, hyperphosphatemia, hyperchloremia, metabolic acidosis, and hypocalcemia. Endocrine and metabolic disorders of CKD comprise hyperuricemia, abnormal lipid metabolism (hypertriglyceridemia, decreased HDL levels), Vitamin D deficiency, and elevated parathyroid hormone levels. A classical manifestation of this is chronic kidney disease-mineral and bone disorder (CKD-MBD), a systemic disorder of mineral and bone metabolism with abnormalities of calcium, phosphorus, PTH, or vitamin D metabolism. Others include abnormalities in gonadal and growth hormones, causing subfertility and impaired growth.[17,18] Hematological abnormalities include anemia, lymphocytopenia, leukopenia, and thrombocytopenia. Anaemia in CKD is usually normocytic normochromic; it arises from multiple factors such as reduced erythropoietin production, decreased life span of red blood cells, and impaired intestinal iron absorption.

Diagnosis: The primary biochemical abnormalities required for the diagnosis of CKD are reduced GFR and proteinuria (albuminuria). The clinical evaluation of individuals suspected of CKD should be targeted at confirming the diagnosis and making an etiological diagnosis to identify the underlying medical condition. KDIGO guideline requires the persistence or progression of detected abnormality for ≥ 3 mo.[15] Evaluating glomerular filtration rate using serum creatinine and a GFR estimating equation such as the CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) and the Modified Diet in Renal Disease (MDRD) equation. The CKD-EPI equation is preferred due to higher precision and accuracy.[19] Diagnosis of CKD based on reduced eGFR requires 2 measurements of eGFR < 60 mL/min/1.73 m2 over 3 months.[17] Further tests such as serum Cystatin C and creatinine clearance are recommended to confirm CKD diagnosis where serum creatinine-based eGFR is deemed unreliable. Cystatin C-based eGFR (eGFRcys) measuring serum Cystatin C is recommended for diagnosis confirmation in adults with isolated reduced eGFRcreat (45–59 mL/min/1.73 m2) without markers of kidney damage.[15] The combined creatinine–cystatin C equation has higher precision and accuracy for GFR estimation than individual equations, providing a more accurate classification of CKD.[20] Albuminuria is characterized by the abnormal presence of albumin in the urine. It is defined as an albumin excretion rate ≥ 30 mg per 24 h, ACR of ≥ 30 mg/g (3 mg/mmol). Urine albumin: creatinine ratio (ACR) is preferred over protein: creatinine ratio (PCR) for detecting low levels of proteinuria due to higher sensitivity. Confirmed ACR ≥ 3mg/mmol is termed clinically significant proteinuria. ACR levels between 3 to 70 mg/mmol should be re-checked and verified using an early morning urine sample.[21] Urinalysis is necessary for the assessment of hematuria. Hematuria 1 + should be investigated further.[21] Aetiological diagnosis is essential for the evaluation of the underlying cause of CKD. These tests include kidney biopsy, renal imaging with an ultrasound scan, CT scan, and MRI, and genetic testing indicated in certain conditions. KDIGO recommends that CKD is classified based on cause, GFR category, and albuminuria category (CGA). This is crucial for prognostication; decreasing eGFR and increasing proteinuria are independently associated with a poorer prognosis of chronic kidney disease.[21]

Overall, the diagnosis and management of CKD rely on assessing various laboratory parameters, including serum creatinine, estimated glomerular filtration rate (eGFR), and albuminuria. However, early diagnosis and management of CKD are crucial to prevent the disease’s progression and reduce the risk of associated complications, such as cardiovascular disease, anemia, and bone disease.

Laboratory abnormalities play a critical role in the diagnosis and management of CKD. Standard laboratory tests used to diagnose CKD include serum creatinine, estimated glomerular filtration rate (eGFR), and urine albumin-creatinine ratio (ACR).

According to the current management guidelines of CKD, a diagnosis of CKD is made when there is evidence of kidney damage or a reduction in kidney function for more than 3 months.^[15] Kidney damage is defined as albuminuria, hematuria, structural abnormalities, or a history of kidney transplantation. A reduction in kidney function is defined as an eGFR of below 60 mL/min/1.73 m2 for more than 3 months.

Serum creatinine is a waste product produced by muscle metabolism and excreted by the kidneys. Elevated serum creatinine levels indicate impaired kidney function and are used to estimate the eGFR, which measures the rate at which the kidneys filter blood. A reduced eGFR is a crucial indicator of CKD.

Serum creatinine is the commonly used laboratory parameter for estimating kidney function. However, its accuracy is affected by various factors such as age, gender, and muscle mass. To address these limitations, eGFR is calculated using equations considering the patient’s age, gender, race, and serum creatinine level. The Modification of Diet in Renal Disease (MDRD) equation is the most commonly used equation.^[15]

Albuminuria is an important marker of kidney damage in CKD. It is a urinary albumin-to-creatinine ratio (ACR) of 30 mg/g or higher. Sometimes, a 24-hour urine collection is used to measure albumin excretion.^[15] Elevated levels of ACR are indicative of kidney damage and are used to monitor the progression of CKD.

In addition to these tests, other laboratory abnormalities may be observed in patients with CKD. These include electrolyte imbalances (such as hyperkalemia and hypocalcemia), anemia, abnormalities in parathyroid hormone (PTH) levels, and phosphate metabolism. The diagnosis and management of CKD are complex and require a multidisciplinary approach. Clinical guidelines provide a framework for healthcare professionals to provide optimal care for patients with CKD. A comprehensive review of current management guidelines for CKD would be essential in determining the most up-to-date and evidence-based approaches for diagnosing and managing CKD. This would include recommendations for laboratory testing and other diagnostic and therapeutic interventions to prevent the progression of the disease and reduce the risk of associated complications. Imaging tests like ultrasound and computerized tomography (CT) scans may also assess the kidneys’ size and shape.

CKD = chronic kidney disease, KDIGO = kidney disease improving global outcome, PTH = parathyroid hormone.