Minimal-Change Glomerulonephritis

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Classification according to ICD-10
N04 Nephrotic Syndrome
N04.0 Nephrotic syndrome, with minimal glomerular lesion
ICD-10 online (WHO version 2019)

The minimal change disease ( MCGN , synonyms: glomerular minimal lesions , lipoid is better the term minimal change glomerulopathy (MCGP) or (English) minimal change disease (MCD), as you all characteristics of inflammation ( itis ) absent) is a renal corpuscle disease and the most common cause of nephrotic syndrome in children ; at the age of under ten the proportion is 90% of the sick, at the age above the proportion is over 50%. In adult nephrotic syndrome, minimal change glomerulonephritis accounts for around 10–15%. The kidney function is usually normal, but may also be limited geringgradig in adults. Acute kidney failure can occur in individual cases .

frequency

Minimal change glomerulonephritis is the most common cause of nephrotic syndrome in childhood. The disease is very common, especially in children aged two to six (90 percent of all nephrotic syndromes). In adults, it is the underlying cause of 10–15 percent of all nephrotic syndromes.

Pathogenesis

Scheme of the changes in a capillary loop of the kidney corpuscle visible under the electron microscope in minimal change glomerulonephritis: Diffuse loss of the foot processes of the glomerular epithelial cells ( podocytes )
dark violet - basement membrane
pink - endothelium
green - visceral epithelium
light violet - mesangium

Minimal change glomerulonephritis may be caused by a T-cell disorder . It is believed that these secrete a cytokine that damages the podocytes of the kidney corpuscle. The cytokine may be interleukin-13 . However, hemopexin or the lymphokine vascular permeability factor (VPF) may also be the cause of podocyte damage .

The damage to the podocytes leads to a reduced synthesis of poly anions such as heparan sulphate , the charge selectivity of the blood-urine barrier decreases; small, negatively charged protein molecules such as albumin are no longer retained in the blood and appear in the urine. The excretion of large, neutral protein molecules, on the other hand, increases only insignificantly; one speaks of selective protein excretion (proteinuria) .

The diffuse loss or flattening of the podocyte foot processes may be due to a decrease in dystroglycans , the adhesion molecules that anchor the podocytes to the glomerular basement membrane .

etiology

The vast majority of minimal change glomerulonephritis are idiopathic , which means that the cause of the disease (etiology) is not known.

In rare cases, however, a cause can be proven:

clinic

The minimal change disease (older name: lipoid) manifested by sudden occurrence of nephrotic syndrome with

In children, the serum creatinine concentration is usually normal, in adults it can also be slightly increased. Blood pressure is often increased in adults . Acute kidney failure can rarely occur.

Diagnosis

The diagnosis is made by a fine tissue examination of kidney tissue , which was obtained by kidney puncture (kidney biopsy) . Under the light microscope , the kidney corpuscles appear normal or show a mild increase in mesangial cells . No immune complexes are detectable in the immunohistochemical examination . The electron microscope shows a diffuse widening and fusion of the foot processes of the podocytes , specialized cells of the kidney corpuscle, which form an important part of the blood-urinary barrier.

The treatment of choice is glucocorticoids , which lead to complete remission of proteinuria in over 90% of cases . Due to the frequency of the disease in childhood and the rapid response to treatment within a few weeks, a diagnosis by kidney biopsy is usually not made in children. In adults, the condition is a rarer cause of nephrotic syndrome and it can take several months for the condition to respond to treatment. Therefore, in adults, prior to starting treatment, the diagnosis must be confirmed by a kidney biopsy.

Other causes of the nephrotic syndrome must be considered in the differential diagnosis . The differentiation from focal-segmental glomerulonephritis , in which the changes in the podocyte foot processes cannot be differentiated from minimal change glomerulonephritis , occasionally presents difficulties . The characteristic, segmental sclerosing changes are not found in all kidney corpuscles in focal segmental glomerulonephritis and may not be detected in a biopsy.

A still controversial special form is the C1q nephropathy . During the immunohistological examination , deposits of the complement component C1q are found in the kidney corpuscles . The disease occurs predominantly in children and young adults. Proteinuria responds poorly to corticosteroids and immunosuppressants , but the prognosis for kidney function is favorable if only minimal glomerular changes are found. Spontaneous remissions with disappearance of the C1q deposits have been described.

therapy

children

Children with nephrotic syndrome have a high likelihood of having minimal change glomerulonephritis. For this reason, prednisone is started in high doses without prior confirmation of the diagnosis by kidney biopsy . One month after protein has disappeared from the urine , the dose of prednisone is first changed to a dose every other day and after a further two months the dose is slowly reduced.

Most children respond to this treatment within four weeks. In 30% of the children no further episode of the nephrotic syndrome occurs, 10–20% have fewer than four relapses, the remaining children have more frequent relapses or a relapse occurs even when the dose of prednisone is reduced.

Alternatively, children with frequent relapses or children whose prednisone can never be completely stopped can be treated with cyclophosphamide for three months to avoid the side effects of prednisone.

Ten percent of children do not respond to prednisone. These children are at increased risk of losing kidney function as the disease progresses. About 20% of children who do not respond to prednisone have a mutation in genes that encode podocyte proteins (NPHS2 gene, WT1 gene). Children who have one of these mutations should not be treated with immunosuppressive agents. Children with no evidence of congenital nephrotic syndrome can be treated with cyclosporine , cyclophosphamide or chlorambucil on a trial basis. If immunosuppressive treatment is unsuccessful or does not make sense, the edema is treated with restriction of salt and fluid intake and with water tablets (diuretics) . Children with persistent nephrotic syndrome are prone to infections and should therefore be vaccinated against pneumococci and varicella .

Adults

If nephrotic syndrome is not treated, life-threatening complications such as blood poisoning or blood clots can occur. Since the nephrotic syndrome is based on a different underlying disease in up to 90% of cases in adults, the diagnosis must be confirmed by kidney biopsy prior to treatment. The treatment of choice is prednisone, which leads to complete resolution ( remission ) of proteinuria in over 90% of adults over several months . The remissions are typically abrupt, that is, the urine is free of protein within two weeks of the initial response to treatment. However, in 50–60% of cases there is a relapse and repeated relapses occur in 10–25% of the affected adults.

Prednisone is given in high doses for three to four months and then slowly reduced over about half a year. Occasional relapses are treated with prednisone for a shorter period of time.

Patients with frequent relapses can be treated with prednisone for a longer period of time if no serious side effects occur. Possibly. Prednisone can then only be taken every other day.

If there are frequent relapses and there are significant side effects of the prednisone, cyclophosphamide or cyclosporine can be used.

If the immunosuppressive treatment is unsuccessful, attempts can be made to reduce protein excretion with ACE inhibitors and / or AT1 antagonists . The fat metabolism disorder is treated with statins . In the case of pronounced nephrotic syndrome, the administration of diuretics and anti-coagulants (anticoagulants) may also be necessary.

forecast

In general, the prognosis for minimal change glomerulonephritis is good. In children, treatment with prednisolone leads to a complete relief of the symptoms of the disease (complete remission ) in about a third of the patients , but in about 30% of those affected, frequent relapses occur (“frequent relapsers”). In these patients or in patients in whom prednisone cannot be discontinued because it would lead to a relapse (steroid-dependent minimal-change glomerulonephritis), 10–40% of those affected can expect the disease into adulthood persists. High blood pressure , osteoporosis , cataracts and changes in the sperm can then occur as complications of the underlying disease or treatment .

literature

  • Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO Clinical Practice Guideline for Glomerulonephritis . In: Kidney Int . Suppl . No. 2 , 2012, p. 139–274 ( clinical guideline English).

Web links

  • Minimal Change Disease - Numerous picture examples in the Atlas of Renal Pathology of the National Kidney Foundation (English)

Individual evidence

  1. ^ JS Cameron: The nephrotic syndrome and its complications . In: Am J Kidney Dis . , 1987 Sep, 10 (3), pp. 157-171, PMID 3307394 . In: A Meyrier: Diagnosis and causes of minimal change disease in adults . UpToDate, as of February 1, 2008.
  2. ↑ A Koyama et al .: A glomerular permeability factor produced by human T cell hybridomas . In: Kidney Int . No. 40 (3) , 1991, pp. 453-460 ( PDF ).
  3. ↑ HK Yap et al .: Th1 and Th2 cytokine mRNA profiles in childhood nephrotic syndrome: evidence for increased IL-13 mRNA expression in relapse . In: J Am Soc Nephrol . No. 10 (3) , 1999, pp. 529-537 ( jasn.asnjournals.org ).
  4. ↑ Ellen T McCarthy, et al .: Circulating permeability factors in idiopathic nephrotic syndrome and focal segmental glomerulosclerosis . In: Clinical Journal of the American Society of Nephrology . 5, No. 11, November 2010, ISSN  1555-905X , pp. 2115-2121. doi : 10.2215 / CJN.03800609 . PMID 20966123 .
  5. ^ A Guasch et al .: Charge selectivity of the glomerular filtration barrier in healthy and nephrotic humans . In: J Clin Invest . No. 92 (5) , 1993, pp. 2274-2282 , PMC 288408 (free full text).
  6. ↑ Glomerular expression of dystroglycans is reduced in minimal change nephrosis but not in focal segmental glomerulosclerosis . In: J Am Soc Nephrol . No. 11 (3) , 2000, pp. 403-412 ( jasn.asnjournals.org ).
  7. ^ Joachim Frey : Nephroses. In: Ludwig Heilmeyer (ed.): Textbook of internal medicine. Springer-Verlag, Berlin / Göttingen / Heidelberg 1955; 2nd edition ibid. 1961, pp. 951-959, here: pp. 951-956 ( lipoid nephrosis ).
  8. ^ M Waldman et al .: Adult minimal-change disease: clinical characteristics, treatment, and outcomes . In: Clin J Am Soc Nephrol . No. 2 (3) , 2007, pp. 445-453 ( abstract ).
  9. ↑ Henriette AC Kyrieleis, Marije M Löwik, Ilse Pronk, Hans RM Cruysberg, Jan AM Kremer, Wim JG Oyen, Bert LP van den Heuvel, Jack FM Wetzels, Elena N Levtchenko: Long-term outcome of biopsy-proven, frequently relapsing minimal -change nephrotic syndrome in children . In: Clinical Journal of the American Society of Nephrology: CJASN . 4, No. 10, October 2009, ISSN  1555-905X , pp. 1593-1600. doi : 10.2215 / CJN.05691108 . PMID 19808243 .