After completing this section, you will be able to outline a systematic approach to patients presenting with renal disease, identifying common causes and risk factors in the Kenyan context, and understanding the rationale behind investigations and initial management. Always check local protocols, Kenya MoH guidelines, and the hospital formulary for specific drug doses and management plans.

Approach to renal disease

Definition

Renal disease encompasses a broad spectrum of conditions that affect the structure and function of the kidneys. This can range from acute kidney injury (AKI), a sudden decline in kidney function, to chronic kidney disease (CKD), a progressive and irreversible loss of kidney function over months to years. Renal disease can manifest as abnormalities in glomerular filtration rate (GFR), proteinuria, haematuria, or structural changes detected on imaging.

Anatomy and physiology you need

The kidneys are retroperitoneal organs responsible for filtering waste products from the blood, regulating fluid and electrolyte balance, producing hormones (erythropoietin, renin, active vitamin D), and maintaining acid-base balance. Key functional units are the nephrons, each comprising a glomerulus and a renal tubule. The glomerulus filters blood under pressure, producing a filtrate that is then processed by the tubules to reabsorb essential substances and secrete waste. GFR is a measure of kidney function, representing the rate at which blood is filtered by the glomeruli.

Causes and risk factors

In Kenya and similar settings, the causes and risk factors for renal disease are diverse and often multifactorial.

• Hypertension: A leading cause of CKD globally and in Kenya, leading to damage of small blood vessels in the kidneys.
• Diabetes Mellitus: Another major contributor, causing diabetic nephropathy through damage to glomerular capillaries.
• Infections:
  • HIV-associated nephropathy (HIVAN): Direct viral effects and immune dysregulation can lead to glomerular damage.
  • Tuberculosis (TB): Renal TB can cause granulomatous inflammation, obstruction, and interstitial nephritis.
  • Malaria: Severe malaria can lead to AKI through haemolysis, microvascular occlusion, and direct tubular injury.
• Rheumatic diseases: Systemic Lupus Erythematosus (SLE) can cause lupus nephritis, an autoimmune glomerulonephritis. Rheumatoid arthritis can be associated with secondary amyloidosis.
• Sickle Cell Disease: Sickle cell nephropathy can occur due to vaso-occlusion in the renal medulla, leading to chronic damage.
• Other Tropical Causes:
  • Schistosomiasis: Chronic infection can lead to granulomatous inflammation and fibrosis in the kidneys.
  • Leptospirosis: Can cause AKI through direct tubular damage and interstitial nephritis.
  • Herbal remedies/Toxins: Unregulated use of traditional medicines or exposure to nephrotoxic agents.
• Obstructive Uropathy: Enlarged prostate, stones, or tumours can impede urine flow, leading to kidney damage.
• Glomerulonephritis: Various forms, including post-infectious glomerulonephritis (e.g., after streptococcal infections), IgA nephropathy.
• Acute Tubular Necrosis (ATN): Often due to ischaemia (e.g., severe dehydration, sepsis) or nephrotoxins.

Pathophysiology

The pathophysiology of renal disease varies greatly depending on the underlying cause. Here are simplified causal steps for common scenarios:

Hypertension leading to CKD: Systemic Hypertension $\rightarrow$ Increased Intraglomerular Pressure $\rightarrow$ Glomerular Endothelial Damage $\rightarrow$ Podocyte Injury $\rightarrow$ Proteinuria $\rightarrow$ Glomerulosclerosis $\rightarrow$ Tubulointerstitial Fibrosis $\rightarrow$ Reduced GFR $\rightarrow$ CKD

Diabetes Mellitus leading to CKD: Hyperglycaemia $\rightarrow$ Advanced Glycation End Products (AGEs) $\rightarrow$ Glomerular Basement Membrane Thickening $\rightarrow$ Mesangial Expansion $\rightarrow$ Glomerular Hyperfiltration $\rightarrow$ Podocyte Damage $\rightarrow$ Proteinuria $\rightarrow$ Glomerulosclerosis $\rightarrow$ Tubulointerstitial Fibrosis $\rightarrow$ Reduced GFR $\rightarrow$ CKD

HIVAN: HIV Infection $\rightarrow$ Direct Viral Effects on Podocytes/Tubular Cells OR Immune Complex Deposition $\rightarrow$ Glomerular Inflammation/Damage $\rightarrow$ Proteinuria $\rightarrow$ Sclerosis $\rightarrow$ Reduced GFR $\rightarrow$ CKD

Acute Tubular Necrosis (ATN) due to Ischaemia: Severe Hypoperfusion/Hypoxia $\rightarrow$ Tubular Epithelial Cell Injury/Necrosis $\rightarrow$ Loss of Tubular Integrity $\rightarrow$ Back-leak of Filtrate $\rightarrow$ Tubular Obstruction (Cellular Debris) $\rightarrow$ Reduced GFR $\rightarrow$ AKI

Clinical features

History

• Presenting Complaint:
  • Oliguria/Anuria: Reduced or absent urine output.
  • Edema: Swelling, particularly in the legs, ankles, face, and periorbital area.
  • Dyspnea: Shortness of breath, especially with exertion or lying flat.
  • Nausea/Vomiting/Malaise: General feeling of being unwell, loss of appetite.
  • Hematuria: Blood in the urine (visible or microscopic).
  • Flank pain: Pain in the side or back.
  • Changes in urine: Foamy, dark, or reduced volume.
  • Symptoms of underlying cause: Fever (infection), joint pain (rheumatic disease), easy bruising (vasculitis).
• Past Medical History:
  • Previous kidney problems, diabetes, hypertension, autoimmune diseases, HIV, TB, malaria, sickle cell disease.
• Medications:
  • Recent use of NSAIDs, certain antibiotics, herbal remedies.
• Social History:
  • Recent travel, exposure to toxins.

Examination Findings

• General Appearance:
  • Pallor: Suggests anemia, common in chronic kidney disease (CKD) due to reduced erythropoietin.
  • Jaundice: May indicate underlying liver disease contributing to renal dysfunction or severe hemolysis.
  • Cachexia: Wasting, seen in advanced CKD or severe systemic illness.
• Vital Signs:
  • Hypertension: Very common, a cause and consequence of kidney disease.
  • Tachycardia: Can be due to anemia, fluid overload, or stress.
  • Tachypnea: Due to fluid overload (pulmonary edema) or metabolic acidosis.
• Head and Neck:
  • Periorbital edema: Early sign of fluid retention.
  • Conjunctival pallor: Suggests anemia.
  • Dry mucous membranes: May indicate dehydration, though fluid overload can also occur.
• Cardiovascular System:
  • Jugular Venous Distension (JVD): Sign of fluid overload.
  • Peripheral edema: Pitting edema in the lower extremities, sacrum.
  • Heart sounds: S3 gallop (volume overload), pericardial rub (uremic pericarditis).
• Respiratory System:
  • Crackles (rales): Indicative of pulmonary edema.
  • Pleural effusion: Fluid accumulation in the pleural space.
• Abdomen:
  • Tenderness: In the flank area (suggesting pyelonephritis or obstruction).
  • Palpable kidneys: Enlarged kidneys can be felt in conditions like polycystic kidney disease or hydronephrosis.
  • Ascites: Fluid in the peritoneal cavity, can be due to nephrotic syndrome or other causes.
• Neurological System:
  • Asterixis (flapping tremor): Sign of uremic encephalopathy.
  • Confusion, lethargy: Uremic encephalopathy.
  • Peripheral neuropathy: Glove-and-stocking distribution, common in long-standing CKD.
• Skin:
  • Pruritus (itching): Due to uremic frost or electrolyte imbalances.
  • Ecchymoses/petechiae: Bleeding tendencies due to platelet dysfunction.
  • Uremic frost: White crystalline deposits on the skin, rare now with dialysis.

Differential diagnosis

Investigations

Diagnosis and severity

Diagnosis is made by integrating history, examination findings, and investigations. The severity is primarily determined by the eGFR and the presence of complications.

• Acute Kidney Injury (AKI): Defined by a rapid decline in kidney function, typically over days to weeks, leading to a rise in serum creatinine and/or a decrease in urine output. Staged based on creatinine rise and urine output.
• Chronic Kidney Disease (CKD): Defined by evidence of kidney damage or an eGFR less than 60 ml/min/1.73m² for 3 months or more. Staged 1-5 based on eGFR, with Stage 5 being kidney failure requiring dialysis or transplant.
• Specific Syndromes: Nephrotic syndrome (heavy proteinuria, hypoalbuminemia, edema, hyperlipidemia) and Nephritic syndrome (hematuria, proteinuria, hypertension, azotemia) are diagnosed based on characteristic clinical and laboratory findings.

Severity is graded using the KDIGO classification for AKI and CKD stages based on eGFR. Complications such as fluid overload, hyperkalemia, metabolic acidosis, anemia, and uremic symptoms indicate more severe disease.

Management

Immediate Stabilisation

The immediate management of acute renal disease focuses on addressing life-threatening complications and stabilising the patient.

• Fluid Overload: If present, manage with fluid restriction and diuretics. In severe cases, dialysis may be required.
• Hyperkalaemia: This is a medical emergency.
  • Stabilisation of Myocardium: Calcium gluconate (intravenous) is used to protect the cardiac membrane from the effects of potassium.
  • Shift Potassium Intracellularly: Insulin and glucose (intravenous), nebulised salbutamol, and sodium bicarbonate (if metabolic acidosis is present) can rapidly shift potassium into cells.
  • Remove Potassium from the Body: Loop diuretics (if urine output is present) and cation-exchange resins can help remove potassium.
• Metabolic Acidosis: Treat with sodium bicarbonate (intravenous) if the serum bicarbonate is significantly low and the patient is symptomatic.
• Uraemic Symptoms: If severe uraemia is present (e.g., pericarditis, encephalopathy, severe nausea/vomiting), urgent dialysis is indicated.
• Hypertension: Aggressively manage severe hypertension with intravenous antihypertensives.

Definitive Treatment

Definitive management depends on the underlying cause of the renal disease.

• Acute Kidney Injury (AKI):
  • Pre-renal: Address the underlying cause of hypoperfusion (e.g., dehydration, sepsis, heart failure).
  • Intrinsic Renal: Treat the specific cause (e.g., antibiotics for pyelonephritis, immunosuppressants for glomerulonephritis, stopping nephrotoxic drugs).
  • Post-renal: Relieve the obstruction (e.g., urinary catheterisation, ureteric stents, nephrostomy).
• Chronic Kidney Disease (CKD): Management aims to slow progression, manage complications, and prepare for renal replacement therapy if necessary.
  • Blood Pressure Control: Target blood pressure is crucial. Angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin II receptor blockers (ARBs) are often first-line, especially in proteinuric disease.
  • Glycaemic Control: Strict control of diabetes is essential.
  • Proteinuria Management: ACEIs/ARBs are key. Dietary protein restriction may be considered.
  • Anaemia Management: Erythropoiesis-stimulating agents (ESAs) and iron supplementation.
  • Mineral and Bone Disorder Management: Phosphate binders, vitamin D analogues, and calcimimetics.
  • Electrolyte Management: Dietary restrictions (potassium, sodium, phosphate) and medications as needed.
  • Vaccinations: Influenza, pneumococcal, and Hepatitis B vaccines are important.

Monitoring and Follow-up

Regular monitoring is vital to assess response to treatment, detect complications, and monitor disease progression.

• Parameters:
  • Renal Function: Serum creatinine, eGFR.
  • Electrolytes: Potassium, sodium, bicarbonate, calcium, phosphate.
  • Fluid Status: Weight, blood pressure, oedema, urine output.
  • Urine Analysis: Proteinuria, haematuria, casts.
  • Blood Pressure: Regular home and clinic monitoring.
  • Haematocrit/Haemoglobin: For anaemia.
  • Bone Metabolism Markers: PTH, calcium, phosphate, alkaline phosphatase.
• Frequency: Varies depending on the severity and cause of the renal disease, ranging from weekly to every few months.

Contraindications and Safety

• Nephrotoxic Agents: Avoidance of NSAIDs, certain antibiotics (aminoglycosides), and contrast media where possible. If unavoidable, careful monitoring of renal function is paramount.
• ACEIs/ARBs: Contraindicated in pregnancy, bilateral renal artery stenosis, and severe hyperkalaemia. Monitor for cough (ACEIs) and angioedema.
• Diuretics: Use with caution in severe dehydration or hypovolaemia.
• Potassium-Sparing Diuretics: Avoid in severe renal impairment or hyperkalaemia.
• Contrast Media: Hydration and N-acetylcysteine may be used to reduce risk in patients undergoing contrast-enhanced imaging.

Complications and Prognosis

Complications:

• Fluid Overload: Leading to pulmonary oedema, hypertension, and heart failure.
• Electrolyte Imbalances: Hyperkalaemia (life-threatening arrhythmias), hyponatraemia, hyperphosphataemia, hypocalcaemia.
• Metabolic Acidosis: Symptoms include fatigue, confusion, and Kussmaul breathing.
• Uraemia: Pericarditis, encephalopathy, gastrointestinal bleeding, pruritus.
• Cardiovascular Disease: Accelerated atherosclerosis, hypertension, left ventricular hypertrophy, arrhythmias.
• Bone Disease: Renal osteodystrophy.
• Anaemia: Due to reduced erythropoietin production and iron deficiency.
• Infections: Increased susceptibility due to impaired immune function.
• Malnutrition: Due to anorexia, nausea, vomiting, and dietary restrictions.
• End-Stage Renal Disease (ESRD): Requiring renal replacement therapy (dialysis or transplantation).

Prognosis:

The prognosis depends heavily on the underlying cause, the severity of renal damage, the presence of comorbidities, and the effectiveness of management. AKI can be reversible, but some cases progress to CKD. CKD is generally progressive, and the rate of progression varies. Early diagnosis and aggressive management of risk factors and complications can significantly improve outcomes and slow disease progression.

High-Yield Exam Points

• Look-alike Conditions:
  • Acute Kidney Injury (AKI) vs. Chronic Kidney Disease (CKD): History (sudden vs. gradual onset), urine output (often reduced in AKI, variable in CKD), ultrasound findings (small, echogenic kidneys in CKD, normal size in AKI unless chronic).
  • Glomerulonephritis vs. Pyelonephritis: Urine microscopy (casts in GN, white cell clumps/pus casts in pyelo), clinical presentation (systemic symptoms in GN, flank pain/fever in pyelo).
• Commonest Wrong First Steps:
  • Aggressively giving IV fluids in fluid overload: Can worsen pulmonary oedema.
  • Starting immunosuppression without confirming the diagnosis: Can be harmful if the cause is not inflammatory or autoimmune.
  • Ignoring hyperkalaemia: Can lead to fatal arrhythmias.
• Examiner at the Bedside:
  • "What is the most likely cause of this patient's renal problem?"
  • "What are the immediate life-threatening complications we need to address?"
  • "What investigations would you like to order next, and why?"
  • "How would you manage this patient's fluid balance?"
  • "What are the long-term implications for this patient?"

Clinical Case

A 55-year-old man presents with a two-week history of worsening fatigue, reduced urine output, and swelling in his legs. He has a known history of poorly controlled diabetes and hypertension. On examination, he is alert but appears unwell. His blood pressure is 170/100 mmHg, pulse is 88 bpm and regular. He has bilateral pitting oedema up to his knees. Auscultation of the chest reveals bibasal crackles. His urine output over the last 24 hours was 300 ml.

Questions:

1. What are the most likely immediate life-threatening complications in this patient?
2. What are the key investigations you would order to assess his renal function and identify the cause?
3. What are the initial management priorities for this patient?

Model Answers:

1. The most likely immediate life-threatening complications are fluid overload (leading to pulmonary oedema and heart failure), hyperkalaemia (leading to arrhythmias), and severe metabolic acidosis.
2. Key investigations include serum electrolytes (especially potassium), serum urea and creatinine (to assess renal function), complete blood count (for anaemia), urinalysis (for protein, blood, casts), and renal ultrasound (to assess kidney size and rule out obstruction). An ECG would also be important to assess for signs of hyperkalaemia.
3. Initial management priorities include fluid restriction, diuretics to manage fluid overload, strict blood pressure control, and urgent correction of any electrolyte abnormalities, particularly hyperkalaemia. If uraemic symptoms are present or severe fluid overload persists, urgent dialysis may be indicated.

Practice Questions

Question 1

A 60-year-old woman with a history of hypertension and diabetes presents with a 3-day history of decreased urine output and generalised weakness. Her serum creatinine is elevated, and her potassium is 6.8 mmol/L. She has no chest pain or shortness of breath. What is the most appropriate immediate management step?

A. Administer intravenous furosemide B. Start an ACE inhibitor C. Administer intravenous calcium gluconate D. Initiate haemodialysis

Answer: C. Administer intravenous calcium gluconate Explanation: The immediate priority in hyperkalaemia is to stabilise the cardiac membrane to prevent life-threatening arrhythmias. Calcium gluconate achieves this.

Question 2

A 45-year-old man with a history of recent streptococcal pharyngitis develops haematuria, generalised oedema, and hypertension. His urinalysis shows red blood cell casts. Which of the following is the most likely diagnosis?

A. IgA nephropathy B. Post-infectious glomerulonephritis C. Minimal change disease D. Membranous nephropathy

Answer: B. Post-infectious glomerulonephritis Explanation: The combination of haematuria, oedema, hypertension, and red blood cell casts following a recent infection is characteristic of post-infectious glomerulonephritis.

Question 3

A 30-year-old woman with known HIV infection presents with a rapid decline in renal function and proteinuria. Her CD4 count is low. What is the most likely renal pathology in this setting?

A. HIV-associated nephropathy (HIVAN) B. Lupus nephritis C. Diabetic nephropathy D. Hypertensive nephrosclerosis

Answer: A. HIV-associated nephropathy (HIVAN) Explanation: HIVAN is a common and aggressive form of kidney disease in individuals with HIV, particularly those with advanced disease and low CD4 counts, presenting with proteinuria and rapid decline in renal function.

Question 4

Which of the following investigations is most useful in differentiating between acute kidney injury (AKI) and chronic kidney disease (CKD) in a patient with a persistently elevated serum creatinine?

A. Serum albumin B. Urine protein-to-creatinine ratio C. Renal ultrasound D. Serum bicarbonate

Answer: C. Renal ultrasound Explanation: A renal ultrasound can reveal characteristic findings of chronicity, such as small, echogenic kidneys, which are typically absent in acute kidney injury.

Question 5

A patient with severe chronic kidney disease is being managed with an ACE inhibitor for proteinuria. They develop a persistent dry cough. What is the most appropriate next step?

A. Increase the dose of the ACE inhibitor B. Add a diuretic C. Switch to an Angiotensin II Receptor Blocker (ARB) D. Investigate for a concurrent infection

Answer: C. Switch to an Angiotensin II Receptor Blocker (ARB) Explanation: A persistent dry cough is a common side effect of ACE inhibitors. ARBs have a similar mechanism of action but do not typically cause cough, making them a suitable alternative.

Drafted with AI assistance from standard references and reviewed for structure. Check details against your lecture notes and the Kenya MoH guideline.