Pyelonephritis and Polycystic Kidneys in a Male Holstein Calf

provide further information about the physiology and pathology of such rare kidney disorders in newborn Holstein calves.


Introduction
Pyelonephritis and cystitis in cattle are bacterial infections that affect the urinary tract and can spread to the kidneys, resulting in inflammation 1 . Many bacteria, such as Corynebacterium (C.) renale, C. pilosum, and C. cystitidis as well as Escherichia coli (E. coli) and Streptococcus spp., Proteus spp., and Staphylococcus spp. are responsible for pyelonephritis and cystitis in cattle 1 . In addition, Mannheimia varigena has been reported to be a cause of pyelonephritis in Holstein calves 2 . Stressful conditions, such as parturition, the peak of lactation, also feeding high-protein diets could predispose cattle to bacterial attacks 1 . Polyuria, hematuria, anorexia, colic, and reduced milk production are common clinical signs in adult animals 1 . Polycystic kidneys might be a heritable disorder in human which exists in two forms 3 . The occurrence of congenital polycystic kidneys has been reported in an inbred herd of springbok 3 . In a study by Inverson et al., all animals with polycystic kidneys had cystic dilatation of the bile duct 3 . Polycystic kidneys in springboks' neonates has been also reported in the literature 4 . It seems that mutation in genes involved in the regulation of the renal tubular epithelial cells plays an important role in the development of polycystic kidneys in both humans and animals 4 . With regard to the environmental and genetic origin of the kidney disorders, observing the kidney complications in a male Holstein calf in the current report may provide insight into diagnosing and preventing such fetal diseases in dairy herds.

Case report
This case was observed in February 2023 in a large commercial dairy farm (Behroozi CO., Tehran, Iran) with approximately 1000 milking cows. A 5-day-old male Holstein calf was first diagnosed with anorexia, lethargy, The internal organs of a Holstein calve aged 90 days old in Iran, 2023. A. Pyelonephritis and polycystic kidneys, B. Lesion on kidney and cystitis, and C. Pus in the lung and fever (41˚C). In addition, the calf had respiratory disease signs (pneumonia) identified by hyperpnea and cough. After diagnosing the calf with fever and pneumonia, 2 mL of dexamethasone, an antiinflammatory drug, and 5 mL of gentamicin, an antibiotic, were administered immediately 1 . The treatment of the calf lasted for 5 days. The calf's appetite, body temperature, and general appearance became better after treatment, but the calf did not become fully healthy. The calf was still lethargic with signs of pneumonia. The growth rate was slower, compared to other calves at the same age. The calf's weakness was significant. The calf's eyes were severely protruded at 60 days of age. The calf finally died at the age of 90 days. Necropsy was performed on the farm to investigate the cause of death. Enlarged, inflamed, and pale kidneys were the main postmortem findings. Both kidneys were inflamed and one of them was polycystic ( Figure 1A). In the other kidney, lesions and inflammation were present ( Figure  1B). Further investigation of the other vital organs revealed severe infection and pus in both lungs ( Figure  1C). Organs, such as the liver and heart were in healthy shape. Inflammations and lesions on the kidneys were apparent ( Figure 1A).

Discussion
Polycystic kidney disease (PKD) might be a congenital disease and characterized by multiple cysts in one or both kidneys. The causes of PKD is mutations in genes regulating the development and function of renal tubular epithelial cells in various species. Polycystic kidney disease is caused by various gene defects that lead to protein dysfunction. This dysfunction results in the dedifferentiation of cells, the proliferation of tubular epithelia, and the excessive secretion of fluid, ultimately causing the formation of renal cysts. It has been reported that PKD is associated with an autosomal dominant and autosomal recessive mode of inheritance due to mutations in different genes 6 . The mutations in the PKD1 and PKD2 genes in autosomal dominant PKD may occur that affecting proteins, which play an important role in the physiology of renal tubular cells, primary cilia, and basal bodies in human 6 . Human autosomal recessive PKD causes cysts in kidneys and the liver and is associated with defects in the PKHD1 gene. Other animals, such as dogs and cats, could develop PKD 7 .
Ascending urinary tract infection mostly causes pyelonephritis in ruminants with Corynebacterium renale or E. coli but hematogenous route is much less common and may result from bacteremia with such agents as Salmonella species or Actinomyces pyogenes 8 .
With respect to the sign of fever in the calf, it seems that bacterial infections may occur in the early stages of life. The existence of cystic areas on both kidneys might be attributed to genetics. It is important to note that the incidence of brucellosis might be the other cause for such a complicated phenomenon. As Brucella spp. attacks trophoblast cells of the placenta 5 , it can affect fetus organ development. Generally, it is suggested that hygiene of the maternity pen and proper disinfection of the umbilical cord alongside optimal transition period's feeding and welfare may be useful in minimizing the congenital disorders in the offspring.

Conclusion
Pyelonephritis and polycystic kidneys can be fatal diseases in neonatal calves. Environment and genetics are the two major factors mediating the occurrence of kidney problems. Routine treatment with antibiotics may not be effective against kidney infections. As a result, prevention is preferred. Nutrition and welfare of cows in late pregnancy have critical effects on the fetus's development. Thus, feeding a balanced diet along with reducing stress in the pregnant cow's environment may decrease the risk of congenital problems in the offspring.