Internal Medicine Nephrology

Diagnosing Chronic Kidney Disease (CKD)

Diagnosing Chronic Kidney Disease (CKD)
Elevated inflammation is a hallmark of chronic kidney disease.

Introduction – Chronic Kidney Disease

The prevalence of chronic kidney disease (CKD) is estimated to be about 10% of the population. There are a large number of elderly patients in primary care with mild CKD but without concomitant albuminuria. Most often, this can be considered normal aging. Moderate CKD is also common in the elderly, especially in concomitant cardiovascular disease and diabetes.

However, renal impairment in combination with albuminuria is a strong and independent risk factor for cardiovascular disease, increasing the renal impairment and also the risk of acute renal failure.

Diagnosis – Chronic Kidney Disease

For the diagnosis of CKD, the patient must have either at least 3 months either renal impairment expressed as eGFR <60 ml/min / 1.73 m or at least one marker for renal injury:

  • Persistent hyperalbuminuria (low grade or high grade)
  • Pathological urinary sediment
  • Pathological anatomy
  • Pathological kidney histology
  • Underwent kidney transplantation

Calculate eGFR according to MDRDCKD-EPI or LM rev based on creatinine or cystatin C. These formulas are considered to be equivalent in accuracy at eGFR> 30 ml/min / 1.73 m 2. Cockcroft & Gault’s equation yields poorer accuracy and should not be used.


From the age of 40 to 50, GFR drops by about 10 ml/min / 1.73 m 2 per 10-year period. Thus, there are a large number of elderly patients in the population with definitive CKD stage 3, i.e. eGFR <60 ml/min / 1.73m 2. CKD 3 without albuminuria carries a moderately increased risk of cardiac, vascular and renal complications compared to healthy peers.

CKD 3 with concomitant low or high albuminuria carries a high to very high risk of cardiovascular mortality, terminal renal failure (CKD 5), acute renal failure and progressive renal disease compared with healthy peers.

Screening – Chronic Kidney Disease

Annual screening for CKD is recommended in the risk groups below. Screen with eGFR and U-albumin-creatinine ratio (U-ACR).

  • Diabetes mellitus
  • Hypertension
  • Signs of cardiovascular disease
  • Albuminuria
  • Hereditary kidney disease, eg polycystic kidney disease
  • Autoimmune system disease
  • Nephrectomized


Creatinine is filtered freely in glomeruli and is excreted to a small extent in tubules. With decreasing glomerular filtration, P-creatinine rises gradually. Creatinine can cause falsely low eGFR in highly muscular individuals, usually men, and falsely high eGFR in the elderly and / or persons with low muscle mass, usually women.


Protein – both kidney disease and fever and physical exertion may result in an increased degree of albuminuria. Check and quantify the albumin degree by U-albumin-creatinine ratio at a calm stage. U-albumin-creatinine ratio is a safer measure of albumin leakage than standard urine. The dipstick measures only albumin. Urinary electrophoresis should be used to examine urinary protein excretion to detect light chains in myeloma.

Glucose – glucosuria occurs mainly in diabetes.

Blood – urine sticks respond to both hemoglobin and myoglobin. If microscopic haematuria is detected without reasonable explanation (such as cystitis, menstruation, postmenopausal urethritis), sediment analysis is a suitable method to distinguish bleeding from glomerular injury. In younger patients with combined proteinuria and macroscopic hematuria, IgA nephritis should be considered.

U-albumin-creatinine ratio (U-ACR)

U-ACR in the morning urine correlates well with results from daily urine collection. Albumin excretion varies with diuresis, increases during the day, and in urinary tract infection and after physical activity. Therefore, for diagnosis of low-grade or high-grade hyperalbuminuria, 2 positive findings are required for 3 consecutive U-ACR controls. The quotient value is multiplied by the number 10 to estimate the daily leakage.

  • U-ACR 3-30 mg / mmol corresponds to albuminuria 30-300 mg / day. It is referred to as low-grade hyperalbuminuria or with an older term, microalbuminuria.
  • U-ACR >30 mg / mmol corresponds to albuminuria >300 mg / day. It is called high-grade hyperalbuminuria or with an older term, macroalbuminuria.

If the degree of albuminuria exceeds 300 mg/mmol, ie 3 g / 24 h, while the patient has edema and hypoalbuminemia, usually <30 g / L, the patient has nephrotic syndrome. Minimal change nephropathy is the most common cause of nephrotic syndrome in children and adolescents. Membranous glomerulonephritis is the most common cause of nephrotic syndrome in adults.

Basal Examination – Chronic Kidney Disease

  1. Determine the CKD stage based on eGFR
  2. Determine the degree of albuminuria
  3. Clarify the cause of CKD

Basal investigation of CKD includes patient history, blood and urine tests and radiological imaging. The prevalence of CKD 3-4 in the population is almost 5%. The basal investigation is recommended in all patients with CKD (regardless of age and gender). Generous referrals for renal ultrasound are particularly important in men over the age of 60 to rule out postrenal obstruction. 

Alternatively, renal visual radiology (eg DT / MR kidney, DT urography or DT / MR abdomen) may have been done previously but on a different indication. If the eGFR is unchanged, and the radiologist has commented on the kidney size, anatomy and occurrence of abnormal findings, you can refrain from a supplementary ultrasound examination of the kidneys.

Etiology of CKD in the elderly often becomes a likelihood assessment (eg, nephrosclerosis due to long-standing hypertension and/or hypercholesterolemia), but may need to be discussed with nephrologists. Patients with CKD who are under 55 years of age should undergo an active study on etiology at the GP clinic and be referred to nephrology specialists based on this algorithm. The algorithm constitutes interdisciplinary decision support for primary care and specialist care.

Medical History

  • Hypertension, arteriosclerosis, obesity?
  • History of ischemic cardiovascular disease?
  • Macroscopic hematuria?
  • Smoking?
  • Diabetes. Retinopathy at the same time?
  • Lower urinary tract symptoms. Suspicion of urinary retention?
  • Recent infection?
  • Error sources for proven albuminuria: morning urine? Previous physical exertion?
  • Previous urinary or renal infections?
  • Ongoing or recently reviewed drug treatment. Possible new drug adjustments?
  • Taking herbal or protein supplements?
  • Family History of kidney disease?
  • Involuntary weight gain or decline last year?
  • Chronic diseases/syndromes?

Physical Examination

  • General appearance including weight
    – Dehydration? Diminished skin turgor? (pinch the thigh skin, should be able to revert within a few seconds). Inspect the tongue and skin over the sternum.
    – Hyperhydration? Lower leg edema? Periorbital edema is usually the sign of hypoalbuminemia.
  • Weight and length. Muscular?
  • Blood pressure, heart, and lungs
    – Pulmonary rales?
    – Neck vein distension?
  • Abdomen
    – Bladder fullness? Enlarged kidneys?
    – Renal bruit (auscultated best 2-3 cm obliquely above the umbilical plane bilaterally)
    – Flank pain?
  • PR
    – Prostate Enlargement?
    – Suspected malignancy?

Radiology – Chronic Kidney Disease

  • Ultrasound Kidney
    – Size? Normal kidneys are 10-12 cm long. At CKD, the renal parenchyma slowly decreases in size. Ultrasound shows small highly-echogenic kidneys in advanced chronic kidney disease. In acute glomerulonephritis, the kidneys may instead be swollen and slightly larger with aberrant echogenicity.

    – Anatomy? Abnormal kidney anatomy may indicate malformation, renal artery stenosis or previous infection. Cystic kidney disease?

    – Obstructions/Strictures? Hydronephrosis?
  • Bladder scan
    – In case of suspected urinary retention

Laboratory Tests – Chronic Kidney Disease

  • Complete Blood Count
    Patients with CKD 4-5 may have an increased bleeding tendency due to poor platelet function. Note that the risk of bleeding is particularly accentuated in the elderly treated with acetylsalicylic acid (ASA). Thus, iron deficiency is not uncommon. Some patients with CKD have increased inflammation, which can also contribute to anemia. At CKD 3b, erythropoietin production begins to decline. However, renal anemia is to be considered as an exclusion diagnosis.
  • Sodium
    Sodium is the most important ion for determining the volume and osmolality of the extracellular fluid. Na concentration is usually normal at CKD 4-5. Hyponatremia may indicate fluid overload.
  • Potassium
    There is an increased risk of hyperkalemia at CKD 4 – 5 which can be accentuated by RAAS blockade, aldosterone antagonists, metabolic acidosis and intake of potassium-rich foods.
  • Creatinine
    See above under heading screening.
  • Albumin
    Hypoalbuminemia can be caused by high-grade hyperalbuminuria with nephrotic syndrome. It can also be a sign of inflammation or malnutrition.
  • Calcium
    Already at CKD 3, the production of active vitamin D in the kidneys begins to decrease, which results in reduced absorption of calcium from the intestine. It leads to hypocalcemia.
  • CRP
    Many patients with CKD have low-grade inflammation, which may be associated with malnutrition and increased atherosclerosis.
  • Urea
    Urea is filtered freely through the glomeruli but is also excreted to a small extent in tubules. With decreasing GFR, urea rises gradually. High urea is partly a sign of low GFR, but may also indicate concomitant high protein intake or increased endogenous protein degradation. Urea concentration in plasma can be reduced by dietary adaptation, the so-called protein-reduced diet, which should always be prescribed by a nephrologist and a medical dietician. Low urea, on the other hand, may be a sign of insufficient protein and energy intake in a patient with low GFR. In these cases, too, the diet should be adjusted by nephrologists and renal nutritionists.
  • Glucose and HbA1c
    Diabetic nephropathy and especially diabetes type 2 is an increasingly common cause of CKD. For diagnosis, U-ACR >3 mg/mmol is required in at least two of three urine samples within six months.
  • Urate
    There is a link between high urate levels and the uremia progression rate. High urate levels should thus be treated, with dose adjustment based on the patient’s age and eGFR.
  • U-ACR
    See above under the heading screening.
  • Urinary
    Protein – See above under the heading “Screening”

    Glucose – See above under the heading “Screening”

    Blood – See above under the heading “Screening”

Complementary laboratory analyses when referral to renal medicine is planned

  • Cystatin C
    Small protein that is formed in almost all body cells. High doses of corticosteroids (in both oral and inhaled form), pregnancy and non-regulated hyperthyroidism increase the level of cystatin C and may produce falsely low eGFR. Untreated hypothyroidism can reduce cystatin C levels and can produce falsely high eGFR.
  • Standard bicarbonate / carbonic acid or base excess
    Kidney acid-base regulation occurs via secretion of hydrogen ions and retention of bicarbonate ions. In decreasing GFR, the tubular secretion of hydrogen ions, as well as the retention of bicarbonate ions, decreases. Metabolic acidosis usually first occurs at CKD 4-5. Metabolic acidosis often causes nocturnal muscle cramps, especially in the legs. Furthermore, the acidosis increases the degradation of the skeletal muscle and increases the risk of muscle atrophy.
  • Phosphate, parathyroid hormone (PTH)
    Already at CKD 3, the production of active vitamin D in the kidneys begins to decrease, which results in reduced intestinal calcium absorption. It leads to hypocalcemia. Furthermore, the kidney’s ability to secrete phosphate decreases, which causes hyperphosphatemia. Hypocalcemia and hyperphosphatemia stimulate the parathyroid glands to increase the production of PTH, to restore balance. These disturbances in the calcium-phosphate balance affect several organs and are a major cause of the increased cardiovascular morbidity and mortality in CKD.

Further Reading