This article provides an overview of rapidly progressive renal failure (RPRF), emphasising the importance of prompt diagnosis and treatment to prevent irreversible end-stage renal disease.

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Rapidly progressive renal failure (RPRF) is a rapid loss of renal function over a very short period of a few days to a few weeks. Since a wide variety of different diseases may present with a similar clinical picture, it is essential to properly work up cases of RPRF so that the exact diagnosis is established.

Time is a valuable factor since if the appropriate treatment is not initiated, the patient may progress to irreversible end-stage renal disease (ESRD) needing life-long renal replacement therapy. RPRF may be considered a 'Renal Emergency'

Aetiology

Primary renal diseases

1. Glomerular disease

• ANCA associated vasculitis
• Post-infectious crescentic glomerulonephritis
• Crescentic IgA nephropathy

2. Tubulointerstitial diseases

• Acute interstitial nephritis
• Acute tubular necrosis

3. Vascular Diseases

• Thromboembolic renovascular disease
• Renal vein thrombosis

Systemic diseases with kidney involvement

1. Systemic vasculitis
2. Multiple myeloma
3. Lupus nephritis class IV
4. Anti-phospholipid antibody syndrome
5. Thrombotic microangiopathy: HUS/TTP
6. Obstructive uropathy: Retroperitoneal fibrosis or pelvic malignancy

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Diagnosis

History and physical examination

There is a rapid decline in renal function over weeks to months, with early clinical features usually non-specific. Sometimes hemoptysis and shortness of breath may be the first clinical feature.

1. Anti-GMB disease may present with pulmonary involvement in the form of diffuse alveolar haemorrhage, and patients present with shortness of breath, cough, and hemoptysis, along with nephritis, hematuria, and oedema.
2. The extrarenal manifestations suggest the presence of immune complex disorders or ANCA vasculitis including:

• General: Fever, night sweat, weight loss, arthralgia
• Oral: Mucosa ulceration
• Eye /Ear: Scleritis, epistaxis, sinusitis, nasal cartilage necrosis
• Respiratory: Shortness of breath, diffuse pulmonary haemorrhage, infiltrate
• GI: Abdominal pain secondary to ischemia, infarction, pancreatitis
• CNS: Mononeuritis multiplex, CNS vasculitis
• Skin: Palpable purpura, ulcer, livedo reticularis

If not addressed promptly, there is a progressive and rapid loss of renal function and, eventually, renal failure. Once renal failure presents, the patient can have fatigue, loss of appetite, nausea, vomiting, decreased urine output (oliguria)

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Investigations

The clinical suspicion, as described in the section of the history and presentation, is backed with the laboratory test for the major causes of rapidly progressive glomerulonephritis:

1. Urinalysis, urine protein, and creatinine ratio: looking for microscopic hematuria and proteinuria. The microscopic examination can further detect the dysmorphic red blood cell characteristics of glomerular hematuria. Proteinuria can suggest sub-nephrotic or nephrotic range proteinuria.
2. Elevated serum creatinine, abnormal electrolyte potassium, magnesium, and calcium
3. CBC with differential: eosinophilia with eosinophilic granulomatosis with polyangiitis
4. Serology for anti-GBM antibody through ELISA or western blot
5. ANCA test: the old test was through indirect immunofluorescence, and its qualitative assay resulted in P-ANCA or C-ANCA
6. Serology to rule post infections: antistreptolysin titer for post-Streptococcus infection, HIV, and Hepatitis B and C serology.
7. Complement C3, C4 level: may be low in some form of granular immune complex disorders causing RPGN like lupus, cryoglobulinemia, and primary MPGN.
8. Serology for lupus: anti-nuclear antibody, ds DNA
9. Other Tests: LDH, platelet, reticulocyte, blood film, anticardiolipin antibody to rule out thrombotic thrombocytopenic purpura (TTP).

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Role of kidney biopsy

One of the most important causes of RPRF is Rapidly Progressive Glomerulonephritis (RPGN). RPGN is a clinic-pathological syndrome; and is characterised clinically by rapid loss of renal function, and pathologically by extensive crescents often with necrosis of the glomerular tuft.

Management

The untreated rapidly progressive glomerulonephritis progresses to rapid loss of renal function over weeks to months. It is very crucial to start treatment as soon as possible.

Empiric treatment is proposed to start before the definitive diagnosis is made, especially in the case where serology and kidney biopsy are delayed due to any reason.

This empiric therapy includes a pulse IV dose of methylprednisolone, either 500 mg or 1 gm, for a minimum of 3 doses. Later more specific treatment is considered once the definitive diagnosis is made.

1. Anti-GBM disease

• An intravenous dose of methylprednisolone followed by oral prednisone
• Cyclophosphamide
• Plasmapheresis

The choice of treatment is plasmapheresis in combination with immunosuppressive agents.

The initiation of treatment as early as possible is the key to the prevention of progressive renal failure.

Plasmapheresis is always followed by immunosuppressive therapy, glucocorticoid, and cyclophosphamide.

2. ANCA positive pauci-immune crescentic glomerulonephritis (GPA & MPA)

• An IV dose of methylprednisolone followed by oral prednisone
• IV or PO cyclophosphamide and/or rituximab
• Plasmapheresis
• Duration of therapy for 3 to 4 months
• Maintenance of therapy is mandatory

The recommended initial treatment is with glucocorticoids with either cyclophosphamide or rituximab with or without plasmapheresis. Plasmapheresis is indicated if there is a rapid deterioration of renal function or severe renal involvement at the time of presentation. Serum creatinine of more than 4 mg/ml or need for dialysis, or there is pulmonary haemorrhage, or if the disease is coexisting anti-GBM antibodies.

3. Immune complex glomerulonephritis

The treatment depends on the aetiology of the associated condition and should be treated accordingly (IgA GN, lupus nephritis, cryoglobulinemia, etc.)

The post-streptococcal GN is usually recovering spontaneously. Very rarely, glucocorticoids are indicated for severely crescentic RPGN.

4. Acute interstitial nephritis

It is usually drug-induced or some other underlying agent. Removal of the inciting cause and iv methylprednisolone is indicated followed by oral steriods.

5. Acute renal vein thrombosis

Typically, initial treatment includes starting unfractionated or low-molecular-weight heparin and then bridged to warfarin, for a goal INR of 2 or 3. Systemic fibrinolysis carries a risk of significant life-threatening bleeding and is usually not recommended. Local thrombolytic therapy with or without catheter-directed thrombectomy is associated with acute renal failure

6. Acute renovascular thrombosis

The first step in management is to initiate anticoagulation with heparin. With the possibility of interventional radiology intervention with local thrombolysis, enoxaparin therapy may be inappropriate. thrombolysis may be indicated should the thrombotic burden be determined through imaging to be significant

7. Multiple myeloma

Dexamethasone, bortezomib and linalidomide are used. Evidence favouring the use of plasmapheresis is limited in cast nephropathy due to a large volume of distribution of light chains resulting in a rapid rebound of light chains after the treatment

8. Thrombotic microangiopathy

The mainstay of treatment in TTP is plasma exchange (PEX) with high-dose corticosteroid therapy. Corticosteroids operate by decreasing the activity of the reticuloendothelial system as well as decreasing autoantibody production. This should be initiated as soon as possible in all patients with unexplained hemolytic anaemia and thrombocytopenia with a normal coagulation profile.

9. Obstructive uropathy

D.J. stenting bilaterally in cases of retroperitoneal fibrosis or percutaneous nephrostomy as needed if stenting is not possible.

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

About the author of this article: Dr Bhavin Mandowara is a practising nephrologist at Zydus Hospital, Ahmedabad.