Course 4 Tubular and vascular nephropathy

Course Overview

• Focus: Hereditary Tubular Nephropathies and associated conditions

Classification of Hereditary Nephropathies

• Hereditary Glomerulopathies: Discussed in Course 3

• Hereditary Interstitial Nephropathies

• Hereditary Tubular Nephropathies: Main focus of this course

• Hereditary Cystic Renal Diseases: Discussed in Course 3

• Hereditary Renal Metabolic Diseases

• Other Rare Renal Diseases: Includes dysplastic diseases and tumors

Hereditary Tubular Nephropathies

• Key Conditions:

  • Fanconi Syndrome: Generalized tubular dysfunction

  • Isolated Tubular Dysfunction

    • Carbohydrate Transport Defect

      • Renal Glycosuria

    • Amino Acid Transport Defects: Hartnup's disease, Cystinuria, Cystinosis

    • Renal Tubular Acidosis (RTA): Includes Classic (Distal) RTA and Proximal RTA

    • Abnormal Water Handling: Nephrogenic Diabetes Insipidus (NDI)

    • Disorders of Sodium Handling: Bartter’s Syndrome, Gitelman’s Syndrome

    • Vitamin D Resistant Rickets

Fanconi Syndrome (Generalized Tubular Dysfunction)

• Clinical Manifestations:

  • Polyuria, polydipsia, dehydration

  • Hypokalaemia leading to impaired concentrating ability

  • Phosphaturia resulting in bone disease:

    • Rickets in children

    • Osteomalacia in adults

    • Osteoporosis

Details on Clinical Features

• Aminoaciduria: All amino acids appear in urine,

  • Excessive levels but no significant clinical sequelae

• Hypercalciuria: Risk of nephrolithiasis/nephrocalcinosis

  • Typically induced by Vitamin D treatment

  • Serum calcium normal

• Renal Tubular Acidosis (RTA): Defective bicarbonate reabsorption causing acidosis

• Glycosuria: Serum glucose usually normal; Fibronyckl syndrome variants may cause hypoglycemia

Additional Electrolyte Imbalances

• Hyponatremia: Can lead to postural hypotension, metabolic alkalosis;

  • Treatment includes salt supplementation

• Hypokalemia:

  • Causes: Na+ reabsorption at the expense of K+, acidosis, volume depletion

  • Clinical features include muscle weakness, constipation, polyuria, arrhythmias

  • Treatment often includes potassium supplementation

Isolated Tubular Defects

• Renal Glycosuria:

  • Reduced glucose reabsorption despite normal blood glucose

  • Typically benign, differentiates from diabetes mellitus

• Aminoaciduria:

  • Originates from metabolic disorders or defective transport mechanisms

  • Cystinuria as a significant condition:

    • Causes recurrent cystine stone formation

    • Managed by addressing genetic mutations affecting amino acid transport

• Phosphaturia: Often leads to:

  • Hypophosphatemia and skeletal disorders

  • Example: X-linked hypophosphatemic rickets

Hereditary Nephrogenic Diabetes Insipidus (NDI)

• Pathogenesis:

  • Rare monogenic, mostly X-linked mutations of AVPR2 gene affecting vasopresin receptor

• Clinical Features:

  • Presents in infancy with significant polyuria and family history

  • Associated with failure to thrive, dehydration, seizures, dilute urine even with hypernatremia

• Treatment Options:

  • Increased water intake

  • Salt restriction

  • Thiazide diuretics combined with amiloride

Bartter's Syndrome

• Overview:

  • Rare disorder, symptoms can appear in neonatal or early childhood

  • Caused by genetic mutations affecting ion transport in Henle’s loop

• Clinical Features:

  • Polyuria, growth retardation, normal/low BP

  • Laboratory findings include hypokalemia, hypochloremic metabolic alkalosis

Gitelman’s Syndrome

• Overview:

  • Genetic mutations of thiazide-sensitive Na-Cl cotransporter

• Clinical Features:

  • Neuromuscular symptoms such as cramps, fatigue, tetany

  • Laboratory values show severe hypomagnesemia, hypokalemia, hypocalciuria

Treatment for Bartter’s and Gitelman’s Syndromes

• Lifelong potassium and magnesium supplementation,

• Increased salt intake,

• High doses of spironolactone

• Use of NSAIDs to reduce polyuria

Renal Vascular Diseases

• Types:

  • Arteriolo-nephrosclerosis: Includes malignant hypertension and benign nephrosclerosis

  • Large-vessel Renal Artery Occlusive Disease: Causes include atherosclerotic renal artery stenosis, fibromuscular dysplasia

  • Atheroembolic Renal Disease

  • Thromboembolic renal disease

Malignant Hypertension**

• Definition: Rapidly progressive BP increases causing severe organ damage.

• Epidemiology:

  • Rare in Western countries; prevalent where treatment is unavailable.

• Clinical Findings:

  • Often presents in African American males; symptoms include headaches, seizures, and dyspnea.

Diagnosis and Prognosis of Malignant Hypertension

• Evolution: Therapy improves vascular manifestations over time.

• Prognosis: Untreated mortality rates >90% within 6-12 months; treatment improves survival rates.

Renal artery occlusive disease**

• Pathophysiology and Clinical Manifestations:

• Progressive renal dysfunction, resistant hypertension, can cause flash pulmonary edema, and increased creatinine post-ACE inhibitors.

Treatment of Renal Vascular Diseases**

• Objective: Blood pressure control, renal function preservation.

• Medical Therapy: Effective for atherosclerotic renal artery stenosis; includes anticoagulation, antihypertensive drugs, and lifestyle management.

Summary**

• Management Options: May include surgical interventions like renal artery angioplasty or bypass in severe cases associated with hypertension. Diagnosis requires a thorough clinical assessment and may include imaging studies as seen with various angiography techniques.