Dr. NK Hase delivers a masterclass on kidney diseases, exclusive in this weekly series for M3 India. In the fourth part, he writes on lower urinary tract lesions, and functional impairment of the kidneys- AKI criteria, AKD, and CKD staging. If you have queries, send in your questions at the end of the article. Dr. Hase will address them in a separate article, once this series concludes.

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Lower urinary tract lesions

The lower urinary tract consists of the urinary bladder, urethral sphincter and urethra. The main function of the bladder is storage of urine and evacuation (voiding) of urine. The bladder is a low pressure reservoir; despite accumulation of urine, the pressure does not increase much. Storage function and evacuation function is maintained by complex neurological connections and viscoelastic properties of the bladder smooth muscle detrusor.

Normal voiding parameter: A normal person may have a sensation of filling, fullness, desire to void and would be able to inhibit voiding until the time and place is appropriate. Once voiding starts, it is a continuous uninterrupted stream. A person will be able to stop stream at will. The normal urine flow rate >15ml/sec. Disturbances can occur in storage or voiding function

Storage symptoms

Symptoms which occur during filling or storage phase of micturition include:

• Increased daytime frequency – A patient's perception that he voids too often by day
• Urgency – A sudden compelling desire to pass urine that is difficult to defer
• Nocturia – The need to wake up at night one or more times to void
• Incontinence – Involuntary leakage
• Nocturnal enuresis.– Involuntary urine leakage during sleep (bed wetting)
• Abnormal bladder sensation

Voiding symptoms

Symptoms experienced during passing (flow) of urine:

1. Hesitancy – Difficulty in initiating act of micturition, resulting in a delay in the onset of micturition after the individual is ready to pass urine
2. Straining to void – An abdominal muscular effort used to initiate, maintain, or improve the urinary stream
3. Slow stream – The individual's perception of reduced urine flow, usually compared with previous performance and sometimes compared with observations of other men
4. Splitting or spraying of the urine stream (double micturition)
5. Intermittent stream or intermittency – Urine flow that stops and starts, on one or more occasions, during micturition
6. Terminal dribble – Prolongation of the final part of micturition, when the flow has slowed to a trickle/dribble
7. Dysuria – Pain, burning sensation, or general discomfort at the time of passing urine

Post-micturition

Post-micturition symptoms include:

• Sense of incomplete evacuation of bladder after the act of micturition
• Post-micturition dribble – The involuntary loss of urine shortly following urination, usually after leaving the toilet

Aetiology: LUTS is usually caused by abnormalities of the prostate, urethra, bladder or sphincter detrusor weakness/overactivity.

Urological causes: Overactive bladder, enlarged prostate, prostatic cancer, urethral stricture, primary bladder neck obstruction, poor contractility of detrusor in elderly and posterior urethral valve, meatal stenosis, hypospadias and phimosis in children.

Neurological causes: Neurogenic bladder due to meningomyelocele, lower spinal cord abnormalities in children, Parkinsonism in adults and the elderly, stroke, spinal cord injuries, multiple sclerosis, and diabetic cystopathy.

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Functional impairment of the kidney

Functional impairment always follows structural damage. The marker functional impairment we routinely use is serum creatinine. Creatinine starts increasing when more than 50% kidney is damaged. Early functional impairment is detected by measuring the Glomerular Filtration Rate.(GFR). Functional impairment may be:

• AKI occurring within 48 hours to 7 days
• Acute kidney Disease (AKD) between 7 to 90 days

Renal impairment may persist more than 90 days, and is called as CKD.

Acute Kidney Injury (AKI) criteria

The kidney disease improving global outcomes (KDIGO) definition is currently followed. The KDIGO guidelines define AKI as follows:

• Increase in serum creatinine by ≥0.3 mg/dL (≥26.5 micromole/L) within 48 hours, or
• Increase in serum creatinine to ≥1.5 times of baseline, which is known or presumed to have occurred within the prior seven days, or
• Urine volume <0.5 ml/kg/hour for six hours

This is valid only after correcting volume status and excluding obstruction.

Stages of AKI (KDIGO)

1. Stage 1 – Increase in serum creatinine to 1.5 to 1.9 times the baseline, or increase in serum creatinine by ≥0.3 mg/dL (≥26.5 micromole/L), or reduction in urine output to <0.5 mL/kg/hour for 6 to 12 hours.
2. Stage 2 – Increase in serum creatinine to 2.0 to 2.9 times the baseline, or reduction in urine output to <0.5 mL/kg/hour for ≥12 hours.
3. Stage 3 – Increase in serum creatinine to 3.0 times baseline, or increase in serum creatinine to ≥4.0 mg/dL (≥353.6 micromole/L), or reduction in urine output to <0.3 mL/kg/hour for ≥24 hours, or anuria for ≥12 hours, or the initiation of renal replacement therapy, or, in patients <18 years, decrease in estimated glomerular filtration rate (eGFR) to <35 mL/min/1.73 m².

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Acute Kidney Disease (AKD)

AKD describes acute or subacute damage and/or loss of kidney function for a duration of between 7 and 90 days after exposure to an AKI initiating event.

AKI and acute kidney disease (AKD) are a continuum, and persistent AKI frequently becomes AKD, defined as a condition wherein criteria for AKI stage 1 or greater persists ≥7 days after an initiating event.

Acute kidney disease stages

1. Stage 0*
   1. A: Absence of criteria for B or C.
   2. B: Continued evidence of ongoing injury, repair and/or regeneration or indicators of loss of renal glomerular or tubular reserve
   3. C: Serum creatinine level <1.5 times the baseline but not back to baseline levels
   4. B/C: Serum creatinine level <1.5 times baseline but not back to baseline levels, and continued evidence of ongoing injury, repair and/or regeneration (*Reflects that even when no apparent residual injury is present, the kidney might be vulnerable for some time after an episode of AKI)
2. Stage 1: Serum creatinine level 1.5 – 1.9 times the baseline
3. Stage 2: Serum creatinine level 2.0 – 2.9 times the baseline
4. Stage 3: Serum creatinine level 3.0 times the baseline or increase in serum creatinine to ≥353.6 μmol/l (≥4.0 mg/dl)‡ or ongoing need for renal replacement therapy

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Chronic Kidney Disease (CKD)

It is defined as abnormalities of kidney structure or function, present for more than 3 months, with implications for health.

The following markers of structural kidney damage (one or more should present and persist for >3 months):

• Albuminuria (AER >30 mg/24 hours; ACR >30 mg/g [>3 mg/mmol])
• Urine sediment abnormalities
• Electrolyte and other abnormalities due to tubular disorders
• Abnormalities detected by histology
• Structural abnormalities detected by imaging
• History of kidney transplantation

The following is the marker of functional impairment (decreased GFR):

• GFR <60 ml/min/1.73 m² (GFR categories G3a–G5)

eGFR is estimated by CKD-EPI creatinine equation.

KDIGO suggests measuring cystatin C in adults with eGFRcreat 45–59 ml/min/1.73 m² who do not have markers of kidney damage if confirmation of CKD is required.

• If eGFRcys/eGFRcreat-cys is also <60 ml/min/1.73 m², the diagnosis of CKD is confirmed
• If eGFRcys/eGFRcreat-cys is >60 ml/min/1.73 m², the diagnosis of CKD is not confirmed

Stages of CKD: Staging of patient with CKD according to GFR, albuminuria can help in management and risk stratification

GFR stages	GFR (mL/min/1.73 m2)	Remarks
G1	≥90	Normal or high markers of structural damage present
G2	60 - 89	Mildly decreased
G3a	45 - 59	Mildly to moderately decreased
G3b	30 - 44	Moderately to severely decreased
G4	15 - 29	Severely decreased
G5	<15	Kidney failure (add D if treated by dialysis)
Albuminuria stages	Albumin excretion rate	Remarks
A1	<30 mg/day	Normal to mildly increased albuminuria (previousy called as microalbuminuria)
A2	30 - 300 mg/day	Moderately increased albuminuria (previously called as microalbuminuria)
A3	>300 mg/day	Severely increased albuminuria (overt proteinuria) non-nephrotic or nephrotic range >3.5 g/day

 

The persistence of the damage or decreased function for at least three months is necessary to distinguish CKD from acute kidney disease. Other findings very specific to diagnose CKD are broad waxy cast in urine, small contracted kidney and presence of renal osteodystrophy.

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Complications of renal impairment

A wide range of disorders may develop as a consequence of the loss of renal function.

Loss of excretory function: Decrease in GFR results in retention of nitrogenous waste product called as azotemia. Azotemia with organ dysfunction is called uremia which usually occurs in a stage of renal failure GFR <10 ml/min.

Manifestations of uremia:

• General symptoms- Fatigue and loss of weight
• Gastrointestinal symptoms- Nausea, vomiting, hiccups, bleeding, uremic fetor (ammonia or urine like odour to the breath)
• Cardiovascular symptoms- Hypertension, pericarditis, pericardial effusion, cardiomyopathy, accleratd atherosclerosis, cardiac failure, coronary artery heart disease
• Respiratory manifeatations- Pleurisy, pleuritis, uremic lung
• CNS manifestations- Fatigue, muscle weakness, malaise, headache, restless legs, asterixis, polyneuritis, mental status changes, muscle cramps, seizures, stupor, and coma (uremic encephalopathy)
• Hematological manifestations- Anaemia, qualitative functional platelet dysfunction, uremic bleeding
• Cutaneous manifestation- Pruritus, uremic frost, white nails, half and half nail
• Impaired immunity- Susceptibility to infection
• Endocrine manifestations- Insulin resistance, growth hormone resistance, increased prolactin, erectile dysfunction and infertility
• Loss of regulatory function: Volume overload, hypertension, pulmonary oedema, hyperkalemia, metabolic acidosis
• CKD MBD: Secondary hyperparathyroidism, renal osteodystrohy, vascular calcification
• Loss of endocrine function- Erythropoietin deficiency anaemia, low 125dihydroxy vitamin D3, hypocalcaemia, hyperphosphatemia, hyper catabolism, chronic inflammation and malnutrition

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To read the previous article in this series, click here.

In the next part, Dr. NK Hase will discuss cases on kidney disease.

Disclaimer- The views and opinions expressed in this article are those of the author's and do not necessarily reflect the official policy or position of M3 India.

The author Dr. NK Hase is a Director clinical Nephrology & Transplant working at Jupiter Hospital, Thane and former Professor & Head of Department of Nephrology Seth GS Medical College and KEM Hospital, Mumbai.