Kidney and Systemic Disease

Introduction

A huge variety of systemic conditions can affect the function of the kidneys, from acute illnesses to drugs and more insidious illnesses.

Diabetic nephropathy

is the commonest cause of end stage renal failure (ESRF) in the developed world (about 3040% of cases of ESRF). Incidence rising in line with diabetes.

Dx Diabetic nephropathy:

Persistent albuminuria >300 mg/day or >200 g/min or urinary albumin:creatinine ratio (ACR) >2.5 mg/mmol in men and >3.5 mg/mmol in women or a urinary albumin concentration >20 mg/l.

Confirmed on at least 2 occasions, 36 months apart.

Continuing decline (penurunan) in the Glomerular

Filtration Rate (GFR).

Elevated arterial blood pressure.

It is more common as a complication of type 1 diabetes mellitus but also affects a significant proportion of type 2 patients. It usually affects patients who have had diabetes for >10 years, with peak incidence of ~3% per year in those who have had diabetes for 1020 years. Patients with albumin secretion of 30300 mg/day to have incipient (baru) nephropathy or microalbuminuria (further defined as albumin excretion >20 g/min). Microalbuminuria can be prevented from progressing to frank diabetic nephropathy by careful management. Without treatment incipient nephropathy usually progresses. The benefits of treatment in cases of established nephropathy are less clear but treatment leads to reduced urinary albumin excretion and, subsequently, a reduced risk of renal impairment or end stage renal disease. Diabetic nephropathy significantly increases the risk of micro and macrovascular complications of diabetes.

Management of diabetic nephropathy: Tight glycaemic control combination of dietary modification, pharmacotherapy (including insulin regimen) and regular physical activity. Tight BP control 130/80 through the use of ACE inhibitors/Angiotensin-2 receptor antagonists diuretics/beta-blockers. ACE inhibitors are of benefit in normotensive diabetics with microalbuminuria. Optimisation of other vascular risk factors through use of aspirin and statins (vastly increased cardiovascular risk caused by diabetic nephropathy). Renal replacement therapy (including transplantation) in those with established kidney disease.

Hypertensive nephropathy/nephrosclerosis particularly so in cases of accelerated or malignant hypertension. Hypertensive nephropathy : 25% with ESRF. Hypertension nephrosclerosis due to ischaemia affecting the glomeruli, and hyperfiltration causing intraglomerular hypertension.

Hypertension also increases the risk of renal failure through the effects of: Cholesterol embolisation to the kidneys Mechanisms of embolisation: Cholesterol crystals dislodge from atherosclerotic embolic shower occlusion of the vessels involved. Localised vasoconstrictive mediators prolong the reaction, leading to progressive, irreversible endorgan damage. The presence of renal artery stenosis (particularly if bilateral) Time : a history of hypertension for about 10 years.

The following factors suggest hypertensive nephrosclerosis as the cause of de novo renal impairment: Commoner in people of African-Caribbean ethnic origin Clinical evidence of hypertensive retinopathy Evidence of left ventricular hypertrophy on ECG History of long-standing or accelerated/malignant hypertension Proteinuria <0.5 g daily Hypertension preceding proteinuria Significant hypertension antecedent to renal failure No evidence of alternative renal/systemic cause for hypertension Renal biopsy histology consistent with nephrosclerosis

Management is through use of a range of anti-hypertensive agents, particularly ACE inhibitors/angiotensin-2 antagonists and diuretics, but other agents are also used. The cohort of patients with hypertensive nephropathy are at risk of bilateral renal artery stenosis which may preclude the use of ACE inhibitors due to worsening of renal function. Close attention to modification of other cardiovascular risk factors and renal replacement therapy are also useful in improving long-term outlook. Revascularisation of the kidneys (via angioplasty/stenting) may be considered in cases of bilateral renal artery stenosis where there is evidence from captopril renography that it is significantly affecting renal function.

Vasculitides

Primary systemic vasculitides a focal necrotising glomerulonephritis RF. cause a pattern of renal disease known as rapidly progressive glomerulonephritis (RPGN). affect medium-sized renal arteries.

Vasculitides that tend to cause renal impairment:

Wegener's granulomatosis (often presents with pulmonary haemorrhage and acute renal failure). Microscopic polyangiitis (formerly known as microscopic polyarteritis nodosa pulmonary infiltrate and RPGN with musculoskeletal/neuropathic/CNS abnormalities). Churg-Strauss syndrome (allergic asthma and eosinophilia with associated renal impairment).

Polyarteritis nodosa (predominant arteritis without significant glomerulonephritis, may manifest as glomerulosclerosis in hypertensive patients).

Renal-limited necrotising crescentic glomerulonephritis A form of microscopic polyangiitis that affects only the kidneys These conditions are usually (8090% of cases) associated w/ ANCA-positive autoantibodies. (anti-neutrophil-cytoplasmic antibody) neutrophils and mononuclear phagocyte cells are activated by ANCA inflammatory attack on blood vessel walls injury to the renal vasculature, similar to the other causes of RPGN (antibodies directed against the glomerular basement membrane or immune complex-mediated damage). There is a rapid impairment renal function with GFR falling by about 50% or so in a period of days to 23 months. Histology : marked fibrinoid necrosis with extensive crescent formation in at least half of all glomeruli. Clinically : flu-like illness with malaise, myalgia, fever, arthralgia, anorexia and weight loss.

Symptoms of renal impairment along with other vasculitic symptoms : abdominal pain, painful skin nodules/ulceration or migratory polyarthralgia. If the upper airways are involved haemoptysis, sinusitis, cough and/or dyspnoea. Management : by systemic immunosuppression combination of high-dose corticosteroid and cyclophosphamide. Azathioprine may be used in place of cyclophosphamide. Renal replacement therapy and plasmapheresis are utilised in the acute phase of the illness.

Systemic lupus erythematosus

termed lupus nephritis; there are many patterns and classifications of disease and some may resemble glomerulonephritis. It is thought that nearly all patients with SLE will have histological evidence of renal involvement, even if it is not causing clinical problems. As therapies for SLE improve prevalence of life-threatening renal disease is falling. formation of immune complexes deposited in the glomerular basement membrane activation of the complement cascade influx of active inflammatory cells.

Around 50% of patients with SLE are affected by lupus nephritis, with 1020% having evidence of lupus nephritis at presentation. Renal impairment may be detected by routine U&E testing in SLE patients, or by the detection of proteinuria which can often be severe enough to cause nephrotic syndrome. Haematuria, also glomerular casts. Renal biopsy confirm the diagnosis. Management : systemic immunosuppression with steroids cyclophosphamide, azathioprine or mycophenolate mofetil. Hypertension to be rigorously controlled: ACE inhibitors. RRT : in severe cases and transplantation may be necessary for end-stage disease, although results are poorer than for nonSLE patients

Progressive systemic sclerosis

also known as scleroderma affect the kidneys through the presence of a microangiopathy a chronic renal impairment, or via the precipitation of a renal crisis. Renal crisis : those patients with diffuse, sudden onset dermatological involvement (the form affecting about a quarter of patients who have systemic sclerosis). Renal crisis affects about 10% of patients with systemic sclerosis. Renal crisis causes accelerated hypertension, oliguric renal impairment, headache, peripheral oedema and fatigue; there is a precipitate rise in urea/creatinine. It tends to occur within the first four years or so of diagnosis (about 75% of cases of renal crisis) but can occur at any time in the course of systemic sclerosis.

The condition can be ameliorated and prevented from progressing to acute renal failure by careful monitoring for its onset, and urgent commencement of treatment with ACE inhibitors. Despite the availability of this therapy, up to 50% of sufferers will progress to acute renal failure. Once established the condition must be treated with renal replacement therapy; some patients will become permanently dependent on dialysis, others may need it temporarily, and remission may occur up to 18 months after starting dialysis.

Sjgren's syndrome

This autoimmune sicca syndrome occurs in association with a range of other autoimmune conditions and can cause renal disease via glomerulonephritis (mesangial proliferative type), interstitial nephritis or renal tubular acidosis. Renal disease affects about 5% of those who suffer Sjgren's syndrome. Typical presenting features for interstitial nephritis include polyuria and renal calculi; it tends to be an early feature of the primary condition. Glomerulonephritis is a late feature of the syndrome and appears to carry a relatively poor prognosis.

Myeloma
Renal failure is a common finding in cases of multiple myeloma, affecting up to about 20% of cases at presentation and up to 50% through the course of the disease. Potential precipitants of renal impairment in myeloma patients: Dehydration and hyperviscosity syndrome Hypercalcaemia Side effects of therapy, especially NSAIDs Tumour lysis syndrome Cast nephropathy Amyloidosis Light-chain deposition disease

The presence of renal failure affect the patient's ability to tolerate chemotherapy modified dosing of melphalan and autologous stem-cell transplantation. Dependence on dialysis is relatively common and some cases are treated by plasma exchange in the acute phase. If myeloma enters complete remission then patients can be considered for renal transplantation.

Sickle cell disease

develop hyposthenuria (inability to form concentrated urine) nocturnal enuresis and polyuria. Acute severe haematuria may occur due to renal papillary necrosis or sickling within the substance of the kidney and is usually treated with epsilon-aminocaproic acid. renal failure was the cause of death in about 20% of cases. causes a glomerulopathy with proteinuria and progressive renal insufficiency leading to ESRF; renal papillary necrosis is another possible mechanism of acute renal syndromes. Albuminuria is a sensitive marker of glomerular damage and precedes the onset of renal failure.

management of the condition in order to reduce the incidence of, and ameliorate, sickling crises effective to prevent the onset of renal failure Great care should be taken to avoid or adjust the dose of nephrotoxic drugs which may precipitate acute or acute on chronic renal impairment. Those with ESRF will require renal replacement therapy and should be considered for transplantation.

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