Approach to Glomerular diseases.DR. YUGANDHAR TUMMALA

Clinical presentation and classification of glomerular diseases

Glomerular diseases present with varying combinations of the following :◦ Proteinuria◦ Hematuria◦ Pyuria◦ Reduced Glomerular filtration rate◦ Reduced excretion of sodiumBased on various combinations glomerular diseases are divided into major clinical syndromes such as◦ Nephrotic syndrome : Proteinuria◦ Acute Nephritic syndrome : Present with all above conditions◦ Rapidly progressive Glomerulonephritis : Present with all above if not RxDialysis dependence◦ Chronic Glomerulonephritis : any of the above lasting for more than 3 months usually combination

Category A : Clinical presentation

Pure Nephrotic illness ( Classically the minimal Change disease)Nephritic illness of mild severity ( Post Streptococcal Acute Glomerulonephritis)Nephritic illness of moderate severity( RPGN/Crescentic Glomerulonephritis )Nephritic- Nephrotic Illness ( MembranoProliferative Glomerulonephritis)

Category B : Glomerular Disease associated With renal dysfunction such asAcute Kidney Injury (AKI)Rapidly Progressive Renal DysfunctionChronic Kidney disease

Category C : Miscellaneous

Non Renal symptoms of Glomerular diseases Pulmonary symptoms : Pulmonary Edema/pulmonary Hemorrhage

Neurological Symptoms : Seizures

Cardiac Symptoms : Pericarditis , CCF

Gastro intestinal Symptoms : Vomiting from Uremia

Rheumatological Symptoms : Arthralgia , Arthritis

Pyrexia of Origin : Collagen vascular diseases , Vasculitis , Endocarditis

Urological symptoms : hematuria

Surgical symptoms : acute abdominal pain of HSP

Endocrine problems : growth failure , Infertility

Based on time of onset of disease : Acute Glomerulo Nephritis : presents from Few Hours to weeks

Rapidly Glomerulo Nephritis : When onset is over few weeks

Chronic Glomerulo Nephritis : Few months

it should not be confused with ARF/CKD

Primary glomerular diseasesMinimal change disease

Idiopathic membranous nephropathy

Primary FSGS

IgA nephropathy

Mesangio Capillary Nephropathy

Acute Post Streptococcal GN

Anti Glomerular Basement membrane disease

Secondary glomerularDiabetic nephropathy

Lupus nephritis

ANCA- Associated vasculitis

Hepatitis B and C related nephropathy

Amyloidosis

Cryoglobulinemia

Alports Syndrome

Secondary FSGS due to Nephron LossSecondary to non glomerular diseases like VUR

Obesity related

Others – Post Nephrectomy : Solitary Kidney FSGS

EtiologyInfections : Bacterial /Prototozoal /viral/ Helminthic

Hereditary : Alports syndrome / Fabrys disease

Multi System : Auto Immune/ vasculitis (SLE/HSP/Cryoglobulinemia)

Systemic Diseases : DM/ amyloidosis

Drugs : NSAIDS/ Allopurinol /gold/Penicillamine /ACE inhibitors

Toxins : vaccines / bee stings

Neoplasia : Multiple myeloma / Ca.Breast

Approach to Diagnosis Step wise Approach

Step 1 : when to suspect

Step 2 : how to categorize the various glomerular disease

Step 3 : characterize the etiology – through various investigations as appropriate

Step 4 : complete the diagnostic arc

Step 5 : treatment and follow up

Step 1 : Suspect glomerular diseases

-By history /Clinical Examination and Urinary Abnormalities.

Proteinuria and Hematuria are not exclusive in Glomerular diseases and can also be seen in Tubular diseases . Hence a Syndromic approach is required

Glomerular Proteinuria : disruption of Glomerular filtration barrier either hereditary/ acquired either renal limited or associated with systemic illness can lead to proteinuria and in particular ALBUMINURIA ( Albumin being the abundant protein ) protein other wise normal is excluded.

Though proteinuria is the hallmark of glomerular proteinuria it may also be seen in Tubular diseases ( less than 1gm/day)

Proteinuria may also be noted when there is over flow

albuminuria Urinary dipstick of 2+ or more ( approx. : 100mg/dl ) indicates albuminuria

How ever false evidences may be seen in cases like

Highly concentrated urine

Alkaline urine

Immediately following exercise

During sepsis

To rule out it 20% sulfa salicylic acid is used and if no turbidity is there then it is false positive

Glomerular HematuriaDisruption to glomerular membrane results in hematuria

It is characterized by presence of dysmorphic red cells or acanthocytes in urine

Greater than 5% urine red cells are characteristic of hematuria

Presence of red cell casts is indicative of Down stream damage to tubules formation of Tamm-horsfall protein.

It can be either isolated as in case of in basement membrane disease or with glomerular proteinuria when a presentation of nephritic syndrome is suspected.

There fore a good urine examination can help in recognize a indeed a glomerular disease.

Step 2 : categorizing glomerular syndrome

Step 3 : Characterizing the glomerular disease by the following : Clinical diagnosis : Nephrotic/ Nephritic /Rapidly progressive/ Isolated urinary abnormalities.Physiological diagnosis: help us to assess renal functionAnatomical diagnosis: help us to rule out other non glomerular pathology.Pathological diagnosis: renal biopsy help us to find out histological types of proliferative glomerulonephritis, Crescentic glomerulonephritis, minimal change disease, membranous nephropathy, proliferative glomerulonephritis.Etiological diagnosis: primary focal segmental glomerulonephritis and secondary due to diabetes, SLE, Hepatitis B and C.Laboratory diagnosis: identification of protein levels, renal parameters, ANA, complement levels, Blood glucose levels.

Step:3- therapeutic approach Management of edema: Restrict fluid, Restrict sodium and initiate Diuretics.

Diet modifications: Restricted salt intake, Fluid restriction, low fat diet.

Manage Hypertension: Diuretics and calcium channel blockers.◦ ACE inhibitors and ARB’s can be managed and help to reduce proteinuria. But to be avoided in acute

renal failure and hyperkalemia◦ Manage glycemic status.◦ Manage lipid abnormalities ◦ Hemodialysis to be initiated, if uremia is worsening.◦ Prevent and treat complications: if pulmonary edema persists-diuretics

◦ Venous thrombosis- heparin and oral anticoagulants◦ Seizures- antiepileptics.◦ Infections- culture specific antibiotics.

Immunosuppression: ◦ Acute glomerular nephritis-no role unless biopsy showed crescents greater than 50%.◦ Minimal change disease- corticosteroids, if not cyclophosphamide.

Immunomodulation: ◦ Levamisole is used in steroid dependent and frequent relapses of Nephrotic syndrome.

Rapidly progressive glomerulonephritis:◦ Cyclophosphamide and plasmapharesis is added with corticosteroids.

Other treatment:◦ Identify the acute factors and treat to stabilize the renal parameters.◦ Manage diabetes and hypertension.◦ Restrict protein intake.◦ Correct fluid status by restricting fluid and salt intake.◦ Correct anemia- identify iron deficiency and use of erythropoietin if iron stores are adequate.◦ Calcium-Phosphorous balance to be maintained.◦ Vitamin D deficiency and hyperparathyroidism to be identified.◦ Hemodialysis and peritoneal dialysis.◦ Renal transplantation.

A systematic approach will help to diagnose glomerular diseases and to preserve the renal function.

Thank you.