Pathophysiology: Renal Disorders

Renal disorders are best understood through what the kidneys normally do and what happens when those functions fail. Healthy kidneys maintain fluid balance, regulate electrolytes and acid base status, excrete metabolic waste and drugs, and act as endocrine organs through renin, erythropoietin, and vitamin D activation. When disease disrupts filtration, tubular handling, or renal blood flow, the consequences are rarely confined to the urinary system. Hypertension, anemia, bone disease, arrhythmias, and systemic inflammation are common downstream effects because the kidneys sit at the center of cardiovascular and metabolic homeostasis.

This article reviews core mechanisms behind acute kidney injury, chronic kidney disease, glomerulonephritis, and major electrolyte disorders, linking each to real world clinical patterns.

Core renal physiology that drives disease

Kidney function depends on three tightly linked processes:

• Glomerular filtration: Plasma water and small solutes pass from glomerular capillaries into Bowman’s space. Filtration depends on renal perfusion pressure, afferent and efferent arteriolar tone, and the integrity of the filtration barrier.
• Tubular reabsorption and secretion: The nephron selectively reabsorbs sodium, water, glucose, bicarbonate, and other solutes, while secreting potassium, hydrogen ions, and organic acids and bases.
• Endocrine signaling: Renin supports blood pressure via the renin angiotensin aldosterone system (RAAS). Erythropoietin drives red blood cell production. The kidney converts 25 hydroxyvitamin D to active 1,25 dihydroxyvitamin D, supporting calcium and phosphate balance.

Most renal pathophysiology is a disruption of perfusion, filtration barrier function, tubular cell health, or long term compensatory responses that become maladaptive.

Acute kidney injury (AKI): abrupt loss of filtration

Acute kidney injury is characterized by a rapid decline in glomerular filtration rate (GFR) with retention of nitrogenous wastes and dysregulation of electrolytes and volume. Pathophysiologically, AKI is often categorized as prerenal, intrinsic, or postrenal, which maps directly to where the primary problem lies.

Prerenal AKI: reduced effective perfusion

Prerenal AKI results from reduced renal blood flow without primary structural damage, at least initially. Common drivers include true volume depletion (hemorrhage, dehydration), decreased cardiac output (heart failure), or systemic vasodilation (sepsis, cirrhosis).

The kidney compensates by increasing RAAS activity and sympathetic tone, constricting efferent arterioles to preserve glomerular pressure, and increasing sodium and water reabsorption. This adaptive response becomes harmful if sustained, because persistent hypoperfusion can progress to ischemic tubular injury.

Intrinsic AKI: parenchymal injury

Intrinsic AKI reflects damage to renal tissue. Major mechanisms include:

• Acute tubular injury (ATI): Often due to ischemia or nephrotoxins. Injured tubular epithelial cells lose polarity, slough into the tubular lumen, and form obstructing casts. Backleak of filtrate and reduced tubular flow further reduce effective GFR. Even when perfusion is restored, recovery depends on tubular cell regeneration and clearance of obstruction.
• Acute interstitial nephritis: Inflammatory injury of the interstitium, frequently drug related, leads to impaired tubular function and reduced filtration through edema and cellular infiltration.
• Glomerular causes: Rapid inflammatory injury of the glomerulus can cause hematuria, proteinuria, and rapid loss of filtration.

Postrenal AKI: urinary tract obstruction

Postrenal AKI arises from obstruction to urine flow, such as prostatic enlargement, ureteral stones, or tumors. Increased tubular pressure opposes filtration, lowering net filtration pressure. Prolonged obstruction triggers interstitial inflammation and fibrosis, converting a potentially reversible problem into chronic damage.

Systemic consequences of AKI

Because the kidneys regulate potassium, acid base balance, and volume, AKI can quickly become life threatening. Hyperkalemia increases arrhythmia risk, metabolic acidosis impairs cardiovascular responsiveness, and salt and water retention may cause pulmonary edema. Uremic toxins contribute to encephalopathy and platelet dysfunction, illustrating how loss of filtration affects multiple organ systems.

Chronic kidney disease (CKD): progressive nephron loss and maladaptation

Chronic kidney disease is defined by persistent kidney damage or reduced GFR over time. Regardless of the initiating cause, CKD progression shares common final pathways: nephron loss, compensatory hyperfiltration in remaining nephrons, and progressive scarring.

Hyperfiltration and glomerulosclerosis

When some nephrons are lost, the remaining nephrons increase single nephron GFR to maintain overall filtration. This requires higher intraglomerular pressure, often mediated by RAAS and preferential efferent arteriolar constriction. Over time, elevated pressure damages the filtration barrier, promoting proteinuria and segmental sclerosis. Protein in the tubular lumen is itself toxic, activating inflammatory and fibrotic pathways in tubular cells and the interstitium.

A simplified way to view declining filtration is: $$\text{GFR}\approx K_f\times \left[(P_{GC}-P_{BS})-({\pi }_{GC}-{\pi }_{BS})\right]$$ where changes in filtration coefficient $K_f$ (from scarring) and glomerular capillary pressure $P_{GC}$ (from hemodynamic adaptation) both shape disease.

Tubulointerstitial fibrosis: the common endpoint

Many CKD etiologies converge on tubulointerstitial fibrosis, characterized by chronic inflammation, fibroblast activation, capillary rarefaction, and extracellular matrix deposition. This reduces oxygen delivery and perpetuates hypoxia, further injuring tubules and accelerating nephron loss.

Systemic consequences of CKD

CKD is a systemic condition with predictable complications:

• Hypertension and fluid overload: Sodium retention and RAAS activation increase intravascular volume and vascular tone.
• Anemia: Reduced erythropoietin production leads to normocytic anemia, contributing to fatigue and worsening cardiac strain.
• Mineral and bone disorder: Phosphate retention and reduced calcitriol lower serum calcium and stimulate secondary hyperparathyroidism. Over time, bone turnover abnormalities and vascular calcification develop.
• Metabolic acidosis: Declining ammoniagenesis and acid excretion cause chronic acidosis, promoting muscle wasting and bone buffering.
• Uremic complications: Accumulation of toxins affects the nervous system, immune function, and hemostasis.

Glomerulonephritis: immune mediated injury to the filtration barrier

Glomerulonephritis (GN) refers to inflammatory diseases of the glomerulus, commonly immune mediated. The key pathophysiologic feature is injury to the glomerular filtration barrier, which consists of fenestrated endothelium, the glomerular basement membrane, and podocytes.

How immune injury produces clinical syndromes

Immune complexes or antibodies trigger complement activation, leukocyte recruitment, and capillary wall injury. The consequences depend on the dominant site and pattern of damage:

• Nephritic pattern: Inflammation narrows capillary lumens and reduces GFR, causing oliguria, azotemia, and hypertension. Damage to capillary walls allows red blood cells to leak into urine, producing hematuria and red cell casts.
• Nephrotic pattern: Podocyte injury and basement membrane disruption increase permeability to proteins, leading to heavy proteinuria, hypoalbuminemia, edema, and hyperlipidemia. Loss of antithrombin and other regulatory proteins increases thrombosis risk.

Some forms of GN progress rapidly, with crescents forming from proliferation of parietal epithelial cells and influx of macrophages into Bowman’s space. Crescents compress the glomerular tuft and can cause swift decline in renal function if not controlled.

Electrolyte disorders in renal disease: mechanisms and patterns

Electrolyte disturbances are not just laboratory abnormalities in renal disorders. They reflect specific failures in filtration, secretion, and hormonal regulation, and they often explain symptoms.

Potassium: impaired secretion and dangerous hyperkalemia

The distal nephron secretes potassium under aldosterone influence. In AKI or advanced CKD, reduced distal flow and reduced functional nephron mass limit potassium excretion. Medications that blunt RAAS signaling can further reduce aldosterone mediated secretion. Hyperkalemia can cause muscle weakness and cardiac conduction abnormalities, making it one of the most urgent metabolic consequences of renal failure.

Sodium and water: dilutional hyponatremia and volume overload

Renal disease frequently impairs free water clearance. When water intake exceeds excretory capacity, serum sodium falls, sometimes with concurrent edema and hypertension due to sodium retention. Conversely, tubular injury can also cause salt wasting in specific settings, illustrating that sodium disorders depend on both GFR and tubular handling.

Acid base balance: metabolic acidosis from reduced net acid excretion

The kidneys reclaim filtered bicarbonate and generate new bicarbonate via ammonium production and titratable acid excretion. Loss of functioning nephrons reduces net acid excretion, leading to metabolic acidosis. Acidosis is not merely a marker of severity; it contributes to bone demineralization, insulin resistance, and muscle catabolism.

Calcium and phosphate: disrupted vitamin D activation and phosphate retention

As GFR declines, phosphate excretion falls, raising serum phosphate and lowering calcium through binding and hormonal responses. At