Table 2

Genetic or acquired conditions causing both kidney disease and stroke

Genetically determined diseasesFeatures
Polycystic kidney diseaseAffects 1 in 400–1000 live births; caused by mutations in PKD1 (Chr16) or PKD2 (Chr4). Renal manifestations include haematuria, hypertension, renal stones, urinary tract infection and progressive renal failure. Subarachnoid haemorrhage may be a complication of ruptured cerebral aneurysms.
COL4A1/A2-related disordersAutosomal dominant type 4 collagen disorders causing a broad spectrum of cerebrovascular disease, including SVD and ischaemic or haemorrhagic stroke; can also be associated with hereditary nephropathy manifesting as proteinuria, haematuria, cysts or CKD.
Fabry’s diseaseX-linked metabolic disorder caused by a deficiency of the enzyme α-galactosidase A. Renal manifestations such as proteinuria, isosthenuria, polyuria and polydipsia or otherwise unexplained renal insufficiency are common. TIAs and strokes occur in 25% of patients with a mean age of onset of 40 years.
Sickle cell anaemiaAutosomal recessive haemoglobinopathy. Renal complications include hyposthenuria, proteinuria, papillary/renal infarcts, hypertension and focal segmental glomerulosclerosis. Vaso-occlusive and haematological crises may result in ischaemic and haemorrhagic strokes, respectively.
Mitochondrial disordersRenal involvement (including CKD, nephrolithiasis, nephrotic syndrome, cysts, renal tubular acidosis, Bartter-like syndrome, Fanconi syndrome, focal segmental glomerulosclerosis, tubulointerstitial nephritis and nephrocalcinosis) has been most frequently reported in patients with mitochondrial encephalomyopathy, lactic acidosis and stroke-like episode (MELAS) syndrome and Kearns-Sayre syndrome.
Acquired conditions
Connective tissue disorders
 Fibromuscular dysplasiaNoninflammatory, nonatherosclerotic disorder that leads to arterial stenosis, occlusion, aneurysm, dissection and arterial tortuosity. The renal and internal carotid arteries are frequently involved.
 Systemic lupus erythematosusUp to 75% of patients may develop lupus nephritis, which can present with proteinuria, haematuria or progressive CKD. Stroke may result from secondary APS or vasculitis.
 Polyarteritis nodosaThe kidneys are the most commonly affected organs, resulting in hypertension, CKD and renal infarctions. Rupture of renal arterial aneurysms can lead to perirenal haematomas. 5%–10% can have central nervous system involvement with subarachnoid haemorrhage or focal infarction.
 ANCA-associatedCharacterised by focal necrotising, crescentic, pauci-immune glomerulonephritis. Ischaemic infarction and intracranial haemorrhage, though rare, can be the initial presentation of ANCA-associated vasculitis and are always associated with significant morbidity
Haematological disorders
 APSRenal disease occurs in a minority of patients with primary disease. Antiphospholipid antibodies also frequently occur in patients with lupus in whom renal disease is more frequently caused by immune deposits. Can cause ischaemic stroke in young patients along with white matter abnormalities and cognitive defects.
 Plasma cell dyscrasiasWaldenström’s macroglobulinaemia is caused by a lymphoplasmacytic lymphoma in the bone marrow with an IgM monoclonal gammopathy in the blood. It can cause proteinuria, nephrotic syndrome and CKD, along with stroke due to a hyperviscosity syndrome.
 CryoglobulinaemiaA type of vasculitis caused by the deposition of circulating cryoglobulins; can be primary or associated with autoimmune diseases, malignancy or infection (particularly hepatitis C). 20% may have glomerulonephritis at presentation. TIAs and stroke can rarely occur.
 Infective endocarditisRenal complications include bacterial infection-related immune complex-mediated glomerulonephritis, renal infarction from septic emboli and cortical necrosis. Symptomatic cerebrovascular complications, including embolic stroke or rupture of mycotic aneurysms, occur in up to 35% of patients.
 HIVCKD secondary to medication nephrotoxicity, HIV-associated nephropathy and immune complex kidney diseases are well described. Potential causes of ischaemic stroke in this setting include HIV-associated vasculopathy, opportunistic infections or neoplasia, cardioembolism and coagulopathy.
 TBGlobally, TB is a common disease, with 8–10 million new cases annually and a rising incidence, particularly in regions with a high incidence of HIV infection. Classical renal TB can present with symptoms suggestive of cystitis with a sterile pyuria. Other features include calyceal distortion, ureteric strictures, bladder fibrosis and interstitial nephritis. It can also cause intracranial vasculitis resulting in stroke.
 Cocaine useCocaine abuse can lead to kidney injury by rhabdomyolysis, vasculitis, infarction, thrombotic microangiopathy and accelerated-phase hypertension. It may also cause stroke through a number of mechanisms, including vasospasm, cerebral vasculitis, enhanced platelet aggregation, cardioembolism and hypertensive surges associated with altered cerebral autoregulation
  • APS, antiphospholipid syndrome; CKD, chronic kidney disease; SVD, small-vessel disease; TB, tuberculosis; TIA, transient ischaemic attack.