Hyperechoic kidneys in a patient with bronchiectasis

Background

The sonographic findings of hyperechoic renal cortices in adults usually indicate chronic renal failure and are associated with reduction in renal size and cortical loss. Hyperechoic renal cortex in a normal-sized or enlarged kidney has a range of causes and this sonographic finding should initiate further investigation. This report describes a patient who presented with worsening renal function in association with normal sized, but hyperechoic kidneys. Biopsy confirmed renal infiltration with amyloid protein, in this case secondary to her longstanding severe bronchiectasis.

Case history

A 72-year-old woman was admitted with respiratory infection, with production of purulent sputum and increasing shortness of breath. She had a longstanding history of bronchiectasis, thought to relate to repeated episodes of childhood pneumonia, and a history of frequent recent hospital admission, necessitating bronchodilators, antibiotics and steroid treatment. She had no other significant medical history.

On examination she had bilateral pitting oedema with blood pressure of 128/70 mmHg, temperature of 37.6°C, respiratory rate of 28 breaths per minute, heart rate of 96 beats per minute and oxygen saturation of 90%. Coarse crackles and wheezing were present on examination of the chest.

Following stable mild renal impairment over many years, her renal function had rapidly and progressively deteriorated over the previous six months (serum creatinine increased from 106 to 280 µmol/L over that period with significant proteinuria and low serum albumin).

Laboratory results showed markedly elevated serum creatinine (280 µmol/L), urea (16 µmol/L) and an estimated glomerular filtration rate (eGFR) of 15 ml/min/1.73m². Erythrocyte sedimentation rate was elevated at 115 mm/h and serum albumin was low (29 g/L). Urine was positive for proteins (albumin 4+) and hematuria (1+). The urine protein creatinine ratio was 1023 (significant proteinuria). There were however no Bence-Jones proteins in the urine.

Serum electrophoresis showed significantly elevated kappa (70.53) and lambda (128.36) light chains; however, the kappa/lambda ratio (0.55) was within normal limits. All other paraproteins were within normal range.

She had negative screening for myeloma and vasculitis and had a normal autoimmune profile. She proceeded to have a renal tract ultrasound scan which demonstrated kidneys that were within normal range at 10.5 cm in length. Bilateral and symmetrical cortical hyperechogenicity was seen (Figures 1 and 2). No hydronephrosis. A simple cyst was evident at the lower pole of the left kidney. Computed tomography demonstrated severe lower lobe bronchiectatic changes (Figure 3).

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Figure 1.

Longitudinal sonogram of normal-sized right kidney. Note hyperechoic cortex (white arrows) compared to adjacent liver (L). Hypoechoic renal pyramids are shown (black arrows).

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Figure 2.

Longitudinal sonogram of normal-sized left kidney. Hyperechoic renal cortex (black arrows). Renal pyramids are indicated with white arrows. Spleen (S) and a lower pole simple renal cyst (C).

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Figure 3.

Axial CT image using a lung window setting, through the lung bases, shows florid bronchiectatic changes. Dilated lower lobe bronchi are present bilaterally (arrows).

Following treatment and nephrology review she underwent an image-guided renal biopsy to evaluate the cause of her worsening renal impairment and renal cortical abnormality.

Renal biopsies showed diffuse, variably segmental and focal nodular expansion of the mesangial matrix by a homogeneous eosinophilic extracellular material consistent with amyloid deposition, which was confirmed with Congo red and immunohistochemical stain (Figures 4 and 5), presumed secondary to her longstanding bronchiectasis. She was referred to a specialist amyloid centre as an in-patient for further follow up and management, but died from complications of renal failure before specialist review.

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Figure 4.

Hematoxylin and eosin stain shows deposition of amyloid (homogeneous eosinophilic material in the glomeruli) (arrowed).

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Figure 5.

(a) Congo red stain without polarisation. (b) Immunohistochemical stains for amyloid. Both stains showing amyloid deposition (arrowed).

Discussion

Ultrasonographically, for the renal cortex to have increased echogenicity, the parenchyma will contain an increase of material able to reflect ultrasound waves. The presence of fibrous tissue, as associated with glomerulosclerosis and interstitial fibrosis, or inflammatory infiltrates, occurring in acute interstitial nephritis and glomerulonephritis, or proteinaceous casts (associated with acute tubular necrosis) will therefore make the kidneys appear hyperechoic. ¹

Typically, the increased echogenicity associated with chronic kidney disease occurs with loss of cortex and reduction in renal size. Preservation of cortex or renal enlargement in association with renal dysfunction has a number of causative pathologies (Table 1). ² Accurate diagnosis is usually only feasible with renal cortical biopsy.

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Table 1.

Differential diagnoses of kidney diseases based on normal/increased echogenicity, kidney size, and reduced kidney function. ²

Increased cortical echogenicity with normal/increased kidney size and reduced renal function
Glomerulonephritis (GN)
Vasculitis
Amyloida
Multiple myeloma
HIV nephropathy
Pre-eclampsia
Tubulo-interstitial disease (e.g. acute interstitial nephritis).

^aAbout half the patients with renal amyloidosis will have atrophic kidneys with renal cortical thinning. ²

Amyloidosis is a rare, multisystem disease characterised by deposition of fibrils in extracellular tissue that involves the kidney, liver, heart, autonomic nervous system and several other organs. ³ The main subtypes of systemic amyloidosis are primary AL amyloidosis, secondary amyloid A (AA) amyloidosis, hereditary amyloidosis and β₂-microglobulin-related amyloidosis. ⁴ Secondary amyloid A (AA) amyloidosis is probably the most common worldwide and it develops as a result of a sustained tissue destructive and chronic inflammatory process. In chronic inflammatory conditions such as bronchiectasis, there is overproduction of both high-density lipoprotein-associated and lipid-free serum amyloid A, due to elevated levels of proinflammatory cytokines (most importantly interleukins 1α, 6 and 8). This serum amyloid A is deposited in tissues and organs, most commonly the kidney, causing tissue toxicity and progressive organ dysfunction. The association between bronchiectasis-related amyloidosis and end-stage renal disease is rare and appears to have been mentioned only in case reports,^5,6 although there is a well-established link.^7,8

Renal involvement is common in patients with systemic amyloidosis, with about half of them dying of renal failure and its complications. ⁹ The signs and symptoms include the appearance of proteinuria, progressive development of renal insufficiency or nephrotic syndrome. ¹⁰ Weakness, weight loss and peripheral oedema are the most common manifestations. The patient we describe had a number of investigations to rule out possible causes of the progressively declining renal function. The serum paraproteins showed no monoclonal preponderance ruling out primary AL amyloidosis. The significantly elevated kappa and lambda light chains were related to persistent inflammation and proinflammatory cytokines. Amyloid deposition can be anywhere in the kidney, but glomerular deposition predominates producing tubular atrophy and interstitial fibrosis, damaging the kidney irreparably.

Imaging findings of renal amyloidosis tend to be non-specific and are not always present, but small and thinned renal cortices are seen in about 50% of patients with systemic amyloidosis indicative of end stage disease. ⁹ In the acute stages, the kidneys may be normal sized or enlarged. Rarely, amyloid deposition may create focal parenchymal lesions. ⁹ Glomerular deposition of amyloid, tubular atrophy and interstitial inflammation cause the increased cortical echogenicity. Although nonspecific, renal ultrasonography findings should prompt further targeted investigations.

The major consequence of renal amyloidosis is progressive renal failure. Currently, there are no available therapeutic agents that can directly target or treat amyloid deposits in tissues. Instead, treatment is aimed at reducing the inflammation caused by the primary disease, which will in turn reduce the circulating levels of amyloid, thus preventing or slowing disease progression.

Conclusion

The key factor in diagnosing secondary amyloidosis is considering the possibility that it is present especially when there is a known chronic inflammatory condition such as bronchiectasis. The ultrasonographic finding of hyperechoic normal-sized kidneys in association with progressive renal impairment should prompt a search for an underlying cause.