Chronic tubulointerstitial kidney diseases N11.-

Chronic tubulointerstitial kidney disease (CTN) can be understood as an unspecific pathological reaction pattern of the kidney to various noxae. Thus, it can develop secondarily as a result of glomerular or vascular damage and thus represents a common final stage of all diseases leading to terminal renal failure. The border between acute and chronic tubulointerstitial nephritis is sometimes blurred. The acute form of the disease can develop into a chronic form (Perazella MA 2017). Certain noxious agents assigned to a CIN can also lead to more acute courses and vice versa (Kisler A 2016). A separate spectrum of interstitial kidney damage is found in transplant kidneys.

• Allergic-toxic due to drugs: especially NSAIDs(analgesic anphropathy) and others (see also acute tubulointerstitial nephritis).
• Metabolic: Hyperuricemia (gout), hypercalcemia, hypokalemia, hyperoxaluria
• Hereditary: Autosomal dominant tubulointerstitial kidney disease (ADTKD), cystinosis, etc.
• Autoimmunological: SLE, Sjögren's syndrome, sarcoidosis (Dong W et al. 2017) polyarteritis nodosa (Hanata N et al. 2017); amyloidosis, IgG4-associated CTN.
• Infectious or obstructive: chronic bacterial phyelonephritis, vesicourethral reflux (VUR).
• Physical: radiation nephritis
• Toxic: lithium nephropathy, heavy metal nephropathy (various substances: e.g. lead and cadmium)
• Hematological: paraproteinemia (multiple myeloma), amyloidosis; AIDs
• Other: Balkan Nephropathy, Chinese Herbs Nephropathy (Chronic tubulointerstitial kidney disease due to chronic poisoning by the vegetable acid "aristolochicacid"); Melamine Nephropathy due to the triamino-azine melamine added (in China) to baby food).
• Chronic interstitial nephritis in agricultural communities: a recently described chronic interstitial (polyetiological) nephritis observed in agricultural communities in South America and Asia (Orantes-Navarro CM et al. 2017).

Slow progressive decrease in glomerular filtration rate (GFR), usually accompanied by moderate tubular proteinuria and occasionally sterile leukocyturia and microhematuria. Often detectable are the signs of tubular dysfunction such as glucosuria, phosphaturia, renal tubular acidosis and reduced urine concentrating ability (possible nocturia).

Routine laboratory tests include: urea, creatinine, urine sediment control; 24-hour urine collection: tubular dysfunction is common, resulting in hematuria and proteinuria (alpha1-microglobulinemia), hyperphosphaturia, aminoaciduria, or glucosuria. Furthermore, high urine pH, metabolic acidosis and salt wasting may be present.

In chronic tubulointerstitial nephritis, tubular atrophy and glomerular changes are observed in addition to mononuclear infiltrates. The chronic form is characterized by interstitial fibrosis and tubule atrophy. Both in the acute and chronic stage, histologically granulomas with giant cells can be seen. They are not pathognomonic for a specific disease (Sjögren's syndrome, sarcoidosis or tuberculosis), but can also be found in drug-induced diseases.

Due to the broad etiological spectrum of chronic tubulointerstitial kidney disease, a careful anamnesis is crucial in patients with renal function deterioration of unclear cause. This should include in particular the question of systemic symptoms, exposure to drugs and toxins, and a detailed and focused family history.

Deposition of triggering noxae. Additional supportive medical measures are often required (supportive therapy of chronic renal insufficiency). The therapy aims to prevent a further deterioration of renal function (up to end-stage renal disease).

Interstitial nephritis got its name due to the inflammatory infiltration of the interstitium and tubules with T cells, macrophages, plasma cells, combined with interstitial edema. Hence the correct name: tubulo-interstitial nephritis.

1. Cohen CD et al (2017) Abnormal kidney function. In: Differential diagnosis of internal diseases. Battegay E. (ed.). Thieme Publishing House Stuttgart S. 475
2. Baldwin DS et al (1968) Renal failure and interstitial nephritis due to penicillin and methicillin. N Engl J Med 279:1245-1252.
3. Dong W et al (2017) Undiagnosed renal sarcoidosis in a patient with chronic interstitial nephritis. Clin Rheumatol 36:2619-2622.
4. Hanata N et al (2017) Polyarteritis nodosa complicated with chronic interstitial nephritis. Int J Rheum Dis 20:1838-1840. https://www.ncbi.nlm.nih.gov/pubmed/26012886
5. Kisler A (2016) Interstitial Nephritis.Swiss Medical Forum 16:108-113
6. Oliva-Damaso N et al (2018) Acute and Chronic Tubulointerstitial Nephritis of Rheumatic Causes. Rheum Dis Clin North Am 44:619-633.
7. Orantes-Navarro CM et al. (2017)Toward a Comprehensive Hypothesis of Chronic Interstitial Nephritis in Agricultural Communities. Adv Chronic Kidney Dis 24:101-106.
8. Perazella MA (2017) Clinical Approach to Diagnosing Acute and Chronic Tubulointerstitial Disease. Adv Chronic Kidney Dis 24:57-63.
9. Sierra F et al (2007) Systematic review: Proton pump inhibitor-associated acute interstitial nephritis. Aliment Pharmacol Ther 26:545-553